Interventions for cutaneous molluscum contagiosum (Review) S

Transcription

Interventions for cutaneous molluscum contagiosum (Review)
van der Wouden JC, van der Sande R, van Suijlekom-Smit LWA, Berger M, Butler CC, Koning
S
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2010, Issue 2
http://www.thecochranelibrary.com
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figure 1.
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ACKNOWLEDGEMENTS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 Topical: 10% Australian lemon myrtle oil vs. vehicle (olive oil), Outcome 1 Complete clearance
or > 90% reduction after 3 weeks. . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.1. Comparison 2 Topical: 5% imiquimod vs. vehicle, Outcome 1 Complete clearance after 4 weeks. . .
Analysis 2.2. Comparison 2 Topical: 5% imiquimod vs. vehicle, Outcome 2 Partial clearance after 4 weeks. . . . .
Analysis 2.3. Comparison 2 Topical: 5% imiquimod vs. vehicle, Outcome 3 Complete clearance after 12 weeks. . .
Analysis 2.4. Comparison 2 Topical: 5% imiquimod vs. vehicle, Outcome 4 Partial clearance after 12 weeks. . . .
Analysis 3.1. Comparison 3 Topical: 10% benzoyl peroxide cream vs. 0.05% tretinoin cream (ITT), Outcome 1 Free of
lesions after 6 weeks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.1. Comparison 4 Topical: 10% KOH vs. saline, Outcome 1 Clinical cure at medium-term follow-up (3
months). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 5.1. Comparison 5 Topical: 10% povidone iodine and 50% salicylic plaster vs. 10% povidone iodine alone,
Outcome 1 Clinical cure at end of study (duration unknown). . . . . . . . . . . . . . . . . .
Analysis 6.1. Comparison 6 Topical: 10% povidone iodine and 50% salicylic acid plaster vs. 50% salicylic plaster alone,
Outcome 1 Clinical cure at end of study (duration unknown). . . . . . . . . . . . . . . . . .
Analysis 7.1. Comparison 7 Topical: 10% povidone iodine vs. 50% salicylic acid plaster, Outcome 1 Clinical cure at end of
study (duration unknown). . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 8.1. Comparison 8 Topical: 5% sodium nitrite in 5% salicylic acid vs. 5% salicylic acid alone, Outcome 1 Clinical
cure at medium-term follow-up (3 months). . . . . . . . . . . . . . . . . . . . . . . .
Analysis 9.1. Comparison 9 Topical: 10% phenol/70% alcohol vs. 70% alcohol (ITT), Outcome 1 Complete clearance at
end of study (max 6 months). . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 10.1. Comparison 10 Topical: 12% salicylic acid vs. 70% alcohol (ITT), Outcome 1 Complete clearance at end of
study (6 months max). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 11.1. Comparison 11 Topical: 12% salicylic acid vs. 10% phenol/70% alcohol (ITT), Outcome 1 Complete
clearance at end of study (max 6 months). . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 12.1. Comparison 12 Systemic: cimetidine vs. placebo, Outcome 1 Clinical cure at medium-term follow-up (4
months). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 13.1. Comparison 13 Systemic: calcarea carbonica vs. placebo, Outcome 1 Improvement at end of study (duration
unknown). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .
INDEX TERMS
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i
[Intervention Review]
Interventions for cutaneous molluscum contagiosum
Johannes C van der Wouden1 , Renske van der Sande1 , Lisette WA van Suijlekom-Smit2 , Marjolein Berger1 , Christopher C Butler3 ,
Sander Koning1
1 Department
of General Practice, Erasmus MC, University Medical Center, Rotterdam, Netherlands. 2 Department of Pediatrics,
Erasmus MC - University Medical Center, Rotterdam, Netherlands. 3 Department of Primary Care and Public Health, School of
Medicine, Cardiff University, Cardiff, UK
Contact address: Johannes C van der Wouden, Department of General Practice, Erasmus MC, University Medical Center, PO Box
2040, Rotterdam, 3000 CA, Netherlands. j.vanderwouden@erasmusmc.nl.
Editorial group: Cochrane Skin Group.
Publication status and date: Edited (no change to conclusions), published in Issue 2, 2010.
Review content assessed as up-to-date: 7 June 2009.
Citation: van der Wouden JC, van der Sande R, van Suijlekom-Smit LWA, Berger M, Butler CC, Koning S. Interventions
for cutaneous molluscum contagiosum. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD004767. DOI:
10.1002/14651858.CD004767.pub3.
ABSTRACT
Background
Molluscum contagiosum is a common skin infection, caused by a pox virus. The infection will usually resolve within months in people
with a normal immune system. Many treatments have been used for molluscum contagiosum but a clear evidence base supporting
them is lacking.
This is an updated version of the original Cochrane Review published in Issue 2, 2006.
Objectives
To assess the effects of management strategies (including waiting for natural resolution) for cutaneous, non-genital molluscum contagiosum in otherwise healthy people.
Search strategy
In June 2009 we updated our searches of the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled
Trials (CENTRAL) in The Cochrane Library (Issue 2, 2009), MEDLINE, EMBASE, and LILACS. We also searched ongoing trials
registers, reference lists, and contacted pharmaceutical companies and experts in the field.
Selection criteria
We investigated randomised controlled trials (RCTs) for the treatment of molluscum contagiosum. We excluded trials on sexually
transmitted molluscum contagiosum and in people with lowered immunity (including those with HIV infection).
Data collection and analysis
Two authors independently selected studies, assessed methodological quality, and extracted data from selected studies.
1
Main results
Eleven studies, with a total number of 495 participants, examined the effects of topical (9 studies), systemic, and homoeopathic
interventions (1 study each). Limited evidence was found for the efficacy of sodium nitrite co-applied with salicylic acid compared to
salicylic acid alone (risk ratio (RR) 3.50, 95% confidence interval (CI) 1.23 to 9.92); for Australian lemon myrtle oil compared to its
vehicle, olive oil (RR 17.88, 95% CI 1.13 to 282.72); and for benzoyl peroxide cream compared to tretinoin (RR 2.20, 95% CI 1.01
to 4.79). No statistically significant differences were found for 10 other comparisons, most of which addressed 2 topical treatments.
Study limitations included no blinding (four studies), many dropouts (three studies), and no intention-to-treat analysis; small study
sizes may have led to important differences being missed. None of the evaluated treatment options were associated with serious adverse
effects.
Authors’ conclusions
No single intervention has been shown to be convincingly effective in the treatment of molluscum contagiosum. The update identified
six new studies, most of them reporting on interventions not included in the original version. However, the conclusions of the review
did not change.
PLAIN LANGUAGE SUMMARY
There is not enough evidence to show that any particular treatment is effective for treating molluscum infection.
Molluscum contagiosum, in healthy people, is a self limiting, relatively harmless viral skin infection. It affects mainly children and
adolescents. It occurs worldwide but is much more frequent in certain geographic areas with warm climates. Molluscum contagiosum
usually presents as single or multiple pimples filled with fluid. People may seek treatment for social and aesthetic reasons and because
of concerns about spreading the disease to others. Treatment is intended to speed up the healing process. Eleven studies with 495
patients were included in this review. This review found that many common treatments for molluscum, such as physical destruction,
have not been adequately evaluated. Several of the treatments that we studied are not part of daily practice. Limitations of several of
these studies were: small numbers of patients, the investigators were not blinded, and patients who did not complete the study (which
were numerous in some studies) were not included in the analysis. None of the evaluated treatment options were associated with serious
adverse effects.
Since most lesions will resolve within months, molluscum contagiosum can be left to heal naturally unless better evidence for the
superiority of other treatment options emerges.
BACKGROUND
Description of the condition
Molluscum contagiosum is a viral skin infection most frequently
encountered in children. The infection is caused by the molluscum
contagiosum virus (MCV), which is classified within the family
of poxviruses (Poxviridae). Infection follows contact with infected
people or contaminated objects. Molluscum contagiosum usually
presents as single or multiple (usually no more than 20) painless,
spherical, shiny, pearly white papules that classically have a central
dimple. Their size may vary from tiny 1 mm papules to large
nodules over 1 cm in diameter (Rogers 1998). The lesions may
itch.
As well as the common form of benign skin tumours (mostly
found in children), there is also a sexually transmitted variant of
molluscum contagiosum which occurs on genital, perineal, pubic, and surrounding skin. Molluscum contagiosum lesions may
also appear in or around the mouth (Whitaker 1991). Molluscum
contagiosum has also been observed with other diseases in people with a damaged immune system (Gottlieb 1994). People with
2
HIV infection are particularly prone to molluscum contagiosum
and prevalence in this population may be as high as 5% to 18%
(Matis 1987; Hira 1988; Husak 1997). The focus of this review
will be the common form of molluscum contagiosum only.
Epidemiology
Molluscum contagiosum occurs worldwide but is much more frequent in certain geographic areas with warm climates, like Fiji,
Congo, and Papua New Guinea. Infection is rare in children under
the age of one year, and typically occurs in the two to five year old
age group (Rogers 1998). The age of peak incidence is reported
as being between the ages of 2 and 3 years in Fiji (Postlethwaite
1967), and between 1 and 4 years in the Congo (formerly Zaire)
(Torfs 1959). In Papua New Guinea the annual attack rate for
children under 10 years of age was 6% (Sturt 1971). For developed countries, population-based occurrence rates are scarce. In
a large questionnaire study among parents of children attending
kindergartens and elementary schools the reported prevalence of
molluscum contagiosum was 5.6% and 7.4% respectively (Niizeki
1984). Much higher prevalence rates have been reported during
outbreaks in closed communities (Overfield 1966).
In the United States, from 1990 to 1999 the estimated number of physician visits for molluscum contagiosum was 280,000
per year (Molino 2004). One out of 6 Dutch children aged 15
years have visited their doctor for molluscum contagiosum at least
once (Koning 1994). There is generally no difference in incidence
between males and females (Sturt 1971; Relyveld 1988; Koning
1994). However, an unequal sex ratio was found in studies from
Japan (Niizeki 1984), Alaska (Overfield 1966), and Fiji (Hawley
1970), where boys were affected more often. This is probably due
to habits associated with the spread of the infection, such as swimming (Postlethwaite 1967; Niizeki 1984). Outbreaks may occur
among children who bathe or swim together. A history of eczema
was found in 62% of children with molluscum contagiosum in
Australia (Braue 2005). In the adolescent and adult age groups
sexual transmission becomes important.
Natural history
The estimated incubation period varies from 14 days to 6 months.
Lesions enlarge slowly and may reach a diameter of 5 to 10 mm in
6 to 12 weeks (Sterling 1998). After trauma (for example, scratching), or spontaneously after several months, inflammatory changes
result in the production of white fluid, crusting, and eventual destruction of the lesions. However, new lesions tend to appear as the
old ones resolve as a consequence of the virus spreading to other
areas of skin. The duration both of the individual lesion and of the
entire episode is highly variable. Crops of molluscum may appear
to come and go for several months, and although most cases are
self limiting and resolve within six to nine months, some may persist for more than three or four years. Follow-up studies (Liveing
1878; Hawley 1970) confirm these figures and show that individual lesions are unlikely to persist for more than two months.
A Japanese study described spontaneous resolution on average 6.5
months after infection in 205 out of 217 children (94.5%) affected
by molluscum contagiosum (Takemura 1983). One month after
the first consultation with the dermatologist, 23% of the children
were cured.
Particularly in atopic people (who are prone to asthma, hay fever,
or eczema), there is a tendency for a patch of eczema (which is
often particularly itchy) to develop around one or more of the lesions a month or more after their onset (De Oreo 1956; Beaulieu
2000). Erythema annulare centrifugum (a widespread rash of red
inflammatory rings) has also been reported (Vasily 1978). Chronic
conjunctivitis and superficial punctate keratitis may similarly complicate lesions on or near the eyelids (Haellmigk 1966; Redmond
2004). The eczema and conjunctivitis subside spontaneously when
the molluscum lesion is removed.
Molluscum contagiosum behaves differently in HIV-infected individuals. As immunodeficiency progresses, molluscum contagiosum becomes more common and resistance to therapy increases.
Frequently, multiple lesions in atypical areas such as the face and
neck can be found. Only limited data are available on the course
of the disease in this group of people.
Description of the intervention
Molluscum contagiosum is a self limiting disease in people with an
uncompromised immune system. Therapy is not necessary for recovery and awaiting spontaneous resolution is an important management strategy. Most lesions resolve within months without scarring in otherwise healthy people (Ordoukhanian 1997). Treatment
is intended to accelerate this process. Destruction of the lesions
and the production of an inflammatory response (Sterling 1998)
are means by which resolution of the lesions could be hastened.
Reasons to treat molluscum contagiosum include:
(a) alleviating discomfort, including itching;
(b) cosmetic reasons;
(c) social stigma associated with many visible lesions;
(d) limiting its spread to other areas of the body and to other
people;
(e) preventing scarring and secondary infection; and
(f ) preventing trauma and bleeding of lesions.
A large number of treatment options are used for molluscum contagiosum. These can be divided into three major categories:
(a) physical destruction of the lesions;
(b) topical agents (i.e. those applied directly to the lesions); and
(c) systemic treatment (i.e. those affecting the whole body).
Physical destruction has been recommended as the preferred
method for treatment of molluscum contagiosum by many authors. Dermatology textbooks mention removal of the lesion with
a sharp curette or the application of liquid nitrogen (cryotherapy) as being simple, painless, and usually effective treatments (
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Sterling 1998; Lowy 1999). Gentle squeezing or pricking with a
sterile needle (Berger 1996) are alternative recommended destructive therapies. Most of these therapies will have to be repeated at
three to four weekly intervals. Treatment may be painful and may
result in scarring (Friedman 1987). Squeezing of lesions may even
lead to the formation of large abscesses due to the disruption of
virus into the deeper layer of the skin (dermis) (Brandrup 1989).
Topical preparations such as podophyllotoxin, liquefied phenol,
tretinoin, cantharidin, or potassium hydroxide can be used to produce a local inflammatory response. In children, prior application
of local anaesthetic cream may reduce the pain of treatment involving physical destruction or local inflammation (Rosdahl 1988;
de Waard 1990), although severe side-effects have been reported
in a case of excessive application of lidocaine-prilocaine (Wieringa
2006). Other proposed topical treatments include immune response modifiers such as imiquimod and cidofovir.
Systemic treatment with cimetidine has been suggested as a possible treatment because of its systemic immunomodulatory effects;
it increases lymphocyte proliferation and inhibits suppressor Tcell function (Orlow 1993; Sterling 1998).
Little data are available with regard to prevailing practice. In the
US, paediatric dermatologists seem to favour cantharidin, imiquimod, and pulsed dye laser, taking into account the age of the
child, number and location of lesions, and input of the parents
(Arbuckle, personal communication). This is different from general practice in the Netherlands, where waiting for natural resolution and physical destruction are the most popular options.
Why it is important to do this review
Molluscum contagiosum is a common reason for consultation in
family practice and dermatology. There are many treatment options available, some of which are painful and some may leave
scars. A decision may be made in favour of active therapy to prevent further spread, relieve symptoms, prevent scarring, and for
cosmetic and social reasons. Indeed, many parents are concerned
about the stigma associated with the lesions. Children with molluscum may be excluded from attending nursery and from participating in physical activities such as swimming. However, the
scientific basis for treatment is unclear. Consequently, many practitioners find themselves in a dilemma as to whether or not to
promote active treatment and, if they do decide on an active treatment strategy, are unclear as to the best option. We have carried
out this systematic review to evaluate treatment options for molluscum contagiosum.
To assess the effects of management strategies, including waiting
for natural resolution, for cutaneous, non-genital molluscum contagiosum in healthy people.
METHODS
Criteria for considering studies for this review
Types of studies
Randomised controlled trials (RCTs) for the treatment of molluscum contagiosum. Trials on sexually transmitted molluscum contagiosum and in people with lowered immunity (including those
with HIV infection) were excluded.
Types of participants
People with a diagnosis of molluscum contagiosum, except for
those with lowered immunity or sexually transmitted molluscum
contagiosum.
In general, treatment is based on a clinical diagnosis only, as molluscum contagiosum is an easy diagnosis to make and confusion
is rare among clinicians. Therefore additional diagnostic criteria,
such as histological examination and laboratory investigations,
were considered unnecessary.
Types of interventions
All treatments aimed at eradicating molluscum contagiosum lesions, including:
•
•
•
•
physical interventions;
systemic treatments;
topical agents; and
awaiting natural resolution.
Studies on other aspects of the treatment of molluscum contagiosum, for example, on reducing pain in the studies that used analgesic EMLA (eutectic mixture of local anaesthetics) cream (Juhlin
1980; de Waard 1990), were excluded.
Types of outcome measures
Primary outcomes
OBJECTIVES
Short-term clinical cure
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One month from last day of treatment, or in the case of different
follow-up durations, the measurement point closest to one month
(plus or minus two weeks).
Clinical cure was defined as complete disappearance of elevated
molluscum contagiosum skin lesions, as assessed by a physician.
Secondary outcomes
(a) Medium and long-term clinical cure (after three months and
six months, respectively)
(b) Medium and long-term improvement (after three months and
six months, respectively)
(c) Time to cure
(d) Recurrences after 3, 6, and 12 months
(e) Adverse effects of treatment such as pain, blistering, sensitisation, scarring, erosion, and pigmentary changes
(f ) Spread to other people
(g) Disease-related quality of life
Measures (b) and (g) were not initially specified in the protocol, but
were added afterwards since improvement at the end of the study
was frequently the most commonly reported outcome measure,
and disease-related quality of life was considered to be a relevant
additional measure.
Search methods for identification of studies
Electronic searches
We updated our searches for relevant trials in the following
databases:
• Cochrane Skin Group Specialised Register (8th June 2009)
using the term mollusca*.
• The Cochrane Central Register of Controlled Trials in The
Cochrane Library Issue 2, 2009 using the search strategy in
Appendix 1.
• MEDLINE (OVID) (from March 2004 to 8th June 2009)
using the search strategy in Appendix 2 which has been
developed from the Cochrane Highly Sensitive Search Strategy
for identifying randomised trials in MEDLINE (Higgins 2008).
• EMBASE (OVID) (from March 2004 to 8th June 2009)
using the search strategy in Appendix 3.
• LILACS (Latin American and Caribbean Health Service
Information database) (from March 2004 to 8th June 2009)
using the strategy in Appendix 4.
Ongoing trials
We searched the following registers of ongoing trials on 30th January 2009 using the term “molluscum”.
• The metaRegister of Controlled Trials www.controlledtrials.com
• The U.S. National Institutes of Health ongoing trials
register www.clinicaltrials.gov
• The Australian and New Zealand Clinical Trials Registry
www.anzctr.org.au
• The World Health Organization International Clinical
Trials Registry platform www.who.int/trialsearch
• The Ongoing Skin Trials register on
www.nottingham.ac.uk/ongoingskintrials
Searching other resources
Reference lists
Reference lists of each selected article or relevant review article
were checked to identify additional studies.
Correspondence
Further relevant published and unpublished trials were obtained
via correspondence with selected pharmaceutical companies and
authors of recent publications.
Language
No language restrictions were imposed.
Data collection and analysis
Selection of studies
Two authors independently read all abstracts or titles of identified trials. If one of the authors considered the article potentially
relevant, a full-text copy of the article was obtained for further
consideration. Two authors independently examined all full-text
copies to determine whether or not they met our inclusion criteria.
Disagreements were resolved by discussion between the authors,
with referral to a third author when necessary.
Trials on sexually transmitted molluscum contagiosum and in people with lowered immunity (including those with HIV infection)
were excluded, in order to increase homogeneity of studies. If the
full-text of studies was not available published abstracts were considered for the review.
If an RCT included a variety of skin diseases, including molluscum
contagiosum, the number of molluscum participants needed to
be at least five in the active treatment and placebo groups. This
criterion was added after the protocol was approved when a study
was found which included 10 molluscum participants with a 9:1
distribution over the 2 treatment groups (Caballero 1996).
5
If the setting of the study was not explicitly mentioned in the text,
it was assumed to be carried out at the affiliation of the first author.
Data extraction and management
Two authors independently carried out data extraction using specially developed and piloted data extraction forms. Discrepancies
were resolved by a third author. Missing data were obtained from
authors where possible. One of the two authors checked and entered the data.
Assessment of risk of bias in included studies
Two authors independently assessed the methodological quality of
the trials. The authors were not blinded to the names of authors,
journals, or institutions.
A third author acted as arbitrator when necessary. The quality
assessment included an evaluation of the following components:
(a) the method of generation of the randomisation sequence;
(b) the method of allocation concealment - it was considered ’adequate’ if the assignment could not be foreseen;
(c) who was blinded/not blinded (participants, clinicians, outcome
assessors);
(d) incomplete outcome data addressed (short, medium, and longterm), scored ’unclear’ if not reported and ’no’ if >20% lost to
follow-up (short-term) or >30% lost to follow-up (long-term) (
Back Review Group 2008);
(e) free of selective reporting;
(f ) free of other bias, such as baseline imbalance, compliance, and
unit of analysis errors in the case of multiple lesions.
Items (d), (e), and (f ) were different from the original protocol or
absent, and adapted for the 2009 update.
Data synthesis
Trials relevant to the focus of this review were examined in greater
detail. We provide a narrative synthesis of included trials, presenting the characteristics of trials and their results.
For studies with a similar type of intervention, meta-analyses were
planned to calculate a weighted treatment effect across trials using
a random-effects model (DerSimonian and Laird model). Similar
comparisons between two interventions were made in only two
studies. For dichotomous outcomes, we expressed the results as risk
ratios (RR) with 95% confidence intervals (CI) and as a number
needed to treat (NNT) where appropriate.
For continuous outcomes, the results were to be expressed as
weighted mean differences (WMD) with 95% CI. For time to
cure as an outcome, the results were to be expressed as weighted
hazard ratios with 95% CI. This was to be achieved by either combining the estimates from the log rank tests (O-E and V) using a
modified version of Peto’s method (Yusuf 1985) or by combining
the log hazard ratio and variance from Cox proportional hazard
models given in the publications using the generic inverse variance
method. Where a mixture of these methods was used for the outcome, the estimates from the log rank tests were to be converted to
log hazard ratios and combined using the generic inverse variance
method. However although this is what we planned to do, no such
studies were found.
Heterogeneity between the studies was to be explored using I²
statistic and, if substantial heterogeneity (I² statistic > 50%) existed
between studies for the primary outcome, reasons for heterogeneity were to be explored, e.g. using sensitivity analyses to examine
the effects of excluding studies with lower reported methodological quality.
Cross-over trials and within-participant designed trials were to be
analysed using techniques appropriate for paired designs, with the
help of a statistician.
RESULTS
Description of studies
See: Characteristics of included studies; Characteristics of excluded
studies; Characteristics of ongoing studies.
Results of the search
For the first version of this review, searches were performed in
March 2004. Seventeen abstracts were generated by searching the
Cochrane Central Register of Controlled Trials database in The
Cochrane LIbrary ; 131 abstracts from MEDLINE, 148 abstracts
from EMBASE, and 45 from LILACS. From these abstracts, some
of which were duplicates, 18 studies were considered possibly to
be RCTs and the full text was obtained. A further 17 studies were
identified from the bibliographies of retrieved studies and the full
text of these studies were also obtained. In November 2008 search
strategies were re-run, 12 additional studies were considered possibly to be RCTs and full text was obtained. The papers discussed
a variety of treatment options for molluscum contagiosum. (See
Table 1 for treatment options for molluscum contagiosum found
in the literature). A further search in June 2009 prior to publication did not yield any new studies.
6
Table 1. Treatment modalities and examples of references
Treatment class
Treatment modality
Surgical treatments
Cryotherapy
Curettage
Topical treatments
Included studies
Other studies
Caballero 1996; Barton 2002;
Salmanpour 2006
Hanna 2006
de Waard 1990
Curettage with punch
Quan 2000
Electric cauterisation
He 2001
Physical expression (squeezing)
Weller 1999
Pricking
Wishart 1903
Pulsed dye laser
Hammes 2001
Acidified nitrite
Ormerod 1999
Australian lemon myrtle oil
Burke 2004
Benzoyl peroxide
Saryazdi 2004
Bromogeramine
Cantharidin
Gräfe 2000
He 2001
Hanna 2006
Funt 1961; Funt 1979; Silverberg
2000; Ross 2004
Cidofovir
Davies 1999; Zabawski 1999;
Toro 2000
Diphencyprone
Kyu 1993; Kang 2005
Griseofulvin
Salmanpour 2006
Imiquimod
Theos 2004; Hanna 2006
Milkweed
Syed 1998; Liota 2000; Barba
2001; Skinner 2002; Bayerl 2003;
Hengge 2003
Behl 1970
Povidone iodine + salicylic acid
Ohkuma 1990
Phenol
Leslie 2005
Podophyllotoxin (HIV patients)
Weller 1999
Syed 1994; Teilla-Hamel 1996;
Markos 2001
7
Table 1. Treatment modalities and examples of references
Potassium hydroxide
(Continued)
Bazza; Short 2006
Retinoic acid
Salicylic acid
Romiti 1999; Romiti 2000
Hund 1975
Ohkuma 1990; Leslie 2005;
Hanna 2006
Salicylic acid combined with Ormerod 1999
sodium nitrite
Silver nitrate
Tretinoin
Niizeki 1999
Saryazdi 2004
Yellow oxide of mercury
Systemic treatments
Combinations of above
Cimetidine
Davis 1896
Antony 2001
Dohil 1996; Cunningham 1998;
Sharma 1998; Yasher 1999
Calcarea carbonica (homeopathy) Manchanda 1997b
Manchanda 1997a
Griseofulvin
Singh 1977
Potassium iodide followed by Xrays
Cope 1915
Most studies were reported in English. However, other languages
included French, Chinese, Japanese, Farsi, and Spanish. Two of
the Japanese papers, the Farsi paper, and a Chinese study were
translated. We read French and Spanish papers in their original
language.
Included studies
Five studies were included in the first version of this review and for
the 2009 update, six more studies were found. Five trials were performed in the UK, three in North America, and three in Asia (see
Characteristics of included studies). The included studies involved
a total of 495 randomised molluscum participants, almost three
times as many as in the first version of the review. The number
of participants in each study ranged from 20 (Manchanda 1997b;
Short 2006) to 124 (Hanna 2006). The number of trial arms was
two in eight of the studies, two studies had three arms (Ohkuma
1990; Leslie 2005), and one had four (Hanna 2006). The number
of patients per trial arm varied from 5 (Ohkuma 1990) to 41 (
Leslie 2005).
Nine of the 11 studies were obtained as full text articles, in two
cases these were unpublished manuscripts (Bazza; Short 2006).
Two studies were available only as published abstracts (Antony
2001; Saryazdi 2004). Additional information was requested and
obtained from the authors of three of the studies (Ohkuma 1990;
Manchanda 1997b; Short 2006). One author did not reply to our
request for additional information (Antony 2001).
Nine of the studies evaluated local therapies for molluscum contagiosum (Bazza; Ohkuma 1990; Ormerod 1999; Short 2006; Burke
2004; Saryazdi 2004; Theos 2004; Leslie 2005; Hanna 2006).
One study included curettage (Hanna 2006).
Two studies investigated systemic treatments (Manchanda 1997b;
Antony 2001). The paper by Manchanda reported on two studies
both making the same comparison but one in a cross-over design
and one in a parallel design. We chose not to include the crossover study because less than five molluscum patients were assigned
to one of the treatment arms.
All included studies were set in hospital outpatient or emergency
8
departments. Only immunocompetent (non-HIV participants)
and non-genital molluscum contagiosum participants were included in the studies. Participants therefore consisted primarily of
children and young adults (adolescents).
Topical therapy
Bazza assessed the effect of 5% potassium hydroxide compared to
0.9% saline. Children with lesions on the left and right side of the
body were included, body halves were randomised into right and
left sides of the body. Treatment was continued for a maximum
period of three weeks. Thirty patients were included in the study,
20 patients (2 to 12 years of age) completed the study.
Burke 2004 assessed the effect of 10% Australian lemon tree oil (n
= 16). The control group (n = 15) received the vehicle, olive oil.
Treatment was continued for 21 days. Mean age of the patients
was 4.6 years.
Hanna 2006 compared four treatments: 5% imiquimod (n = 29),
0.7% cantharidin (n = 30), 16.7% salicylic acid/16.7% lactic acid
(n = 29), and curettage (physical destruction, n = 31). Treatment
frequency varied, treatment duration was not reported, nor was
the moment at which patients were cured. Participants were aged
between 1 and 16 years of age.
Leslie 2005 compared the effect of 10% phenol/70% alcohol (n
= 41) to 12% salicylic acid (n = 37) and to 70% alcohol (n =
36). Treatment frequency varied. Patients returned for additional
treatment for up to six months. Age of the participants varied from
1 to 15 years.
Ohkuma 1990 assessed the effect of application of 10% povidone
iodine solution combined with 50% salicylic acid plaster. Treatment was continued until resolution of the lesions. There were
three intervention arms, 10% povidone iodine solution combined
with 50% salicylic acid plaster (n = 20), povidone iodine alone
(n= 5) and salicylic plaster alone (n = 10). Participants were aged
between two and nine years.
Ormerod 1999 assessed the effect of 5% sodium nitrite co-applied
daily with 5% salicylic acid, under occlusion (n = 16). A control
group received an identical cream with 5% salicylic acid but without sodium nitrite (n = 14). Treatment was for three months or
until participants were cured or dropped out if sooner. Thirty participants with a median age of six years participated in this study.
Saryazdi 2004 compared the effect of 10% benzoyl peroxide cream
with 0.05% tretinoin cream. Participants were children, their age
was not specified. The total number of patients was 30, we assumed
these were equally divided among the 2 treatments. Outcomes are
reported for week 6.
Short 2006 assessed the application of a 10% potassium hydroxide
solution (n = 10). The control group received saline (n = 10). The
age of included participants ranged from 2 to 12 years. Assessment
of the therapeutic response took place up to 90 days after start of
treatment or 1 month after clearance, or both.
Theos 2004 assessed the effect of imiquimod 5% (n = 12). Eleven
patients received a vehicle cream, up to 12 weeks. The age of the
participants in the study varied from one to nine years. Participants
were assessed every 2 weeks after treatment initiation, up to 12
weeks.
Systemic therapy
Antony 2001 assessed the effect of 35 mg/kg/day of cimetidine
given once daily as an oral suspension for three months. Thirtyeight participants, aged 1 to 16 years, were enrolled in the trial,
but assignment details were only given for the 19 participants
who completed the study. Eight of these were randomised into
the treatment arm of the trial. The 11 participants in the control
arm received a matched oral suspension. The follow-up period was
four months from the start of treatment.
Manchanda 1997b evaluated different potencies of a homoeopathic drug called calcarea carbonica given daily for 15 days (n =
14). Six participants were randomised to receive plain sugar globules as a placebo. Participants’ ages ranged from 0 to 30 years.
Follow-up duration was not reported.
Excluded studies
In the original review, 30 of the 35 studies did not fulfil our criteria.
In the update, 6 of the 12 studies that were obtained as full text
papers were excluded. The most common reasons for exclusion
were case series rather than RCTs, or because the participant groups
were outside the focus of the review (see Characteristics of excluded
studies).
Risk of bias in included studies
The ’Risk of bias’ table gives the results of the quality assessment
for each included study (see Characteristics of included studies).
Method of generation of randomisation sequence
Nine of the eleven studies were described in the text as randomised
trials (Bazza; Ormerod 1999; Antony 2001; Short 2006; Burke
2004; Saryazdi 2004; Theos 2004; Leslie 2005; Hanna 2006).
Additional information was obtained from the authors of the
other papers, who confirmed in writing that the participants were
randomised into the different treatment groups (Ohkuma 1990;
Manchanda 1997b). The way the randomisation sequence was
generated was described in only three of the papers (Burke 2004;
Leslie 2005; Hanna 2006). In a personal communication, Manchanda informed us that in his study this was ’generated manually’.
Allocation
Only one of the papers (Burke 2004) described whether the investigators took any precautions to conceal the allocation schedule
from those involved in entering participants into the study.
9
Blinding
Seven of the studies were described as double-blind (Bazza;
Manchanda 1997b; Ormerod 1999; Antony 2001; Short 2006;
Burke 2004; Theos 2004). However, none of them provided information about the visual similarity of treatments, nor whether
blinding was maintained throughout follow-up. Ormerod reported brown staining on the skin in six participants with active
treatment, but none of the controls, which may have unblinded
the assessment of outcomes (Ormerod 1999).
Incomplete outcome data
Two studies did not report any loss to follow-up (Ohkuma 1990;
Saryazdi 2004). Only three studies provided information on incomplete outcome data for short-term outcomes (Short 2006;
Burke 2004; Theos 2004) and three for medium or long-term outcomes (Manchanda 1997b; Short 2006; Theos 2004). Saryazdi
2004 reported that efficacy was assessed at 2, 4, and 6 weeks but
only provided results at week 6.
Effects of interventions
Primary outcome: complete clearance after one
month
The primary outcome for this review was complete disappearance of elevated molluscum contagiosum lesions after one month.
Three studies, all identified during the 2009 update, reported on
this outcome after 3 to 6 weeks.
Topical treatments (Analyses 1 to 3)
Application of 10% Australian lemon tree oil resulted in complete
disappearance (or > 90% of lesions) after three weeks in 9/16 patients versus 0/15 of the control group who received only the vehicle (olive oil) (Relative Risk (RR) 17.88, 95% confidence interval
(CI) 1.13 to 282.72; p = 0.04) (Analysis 1.1) (Burke 2004).
Application of 5% imiquimod cream resulted in complete clearance in 2/12 patients versus 0/11 of the control group who received vehicle cream (RR 4.62, 95% CI 0.25 to 86.72) (Analysis
2.1) (Theos 2004). Partial clearance was observed in 7/12 versus
0/11 patients (RR 13.85, 95% CI 0.88 to 217.26) (Analysis 2.2).
None of these were statistically significant.
Application of 10% benzoyl peroxide resulted in complete disappearance of lesions after six weeks in 11/15 patients versus 5/15 of
the group who received 0.05% tretinoin (RR 2.20, 95% CI 1.01
to 4.79; p = 0.05) (Analysis 3.1) (Saryazdi 2004).
Secondary outcomes: medium and long term cure;
time to cure; adverse effects
Five studies reported on medium term clinical cure (after three or
four months) (Bazza; Ormerod 1999; Antony 2001; Short 2006;
Theos 2004) and two on time to cure (Ohkuma 1990; Short
2006), but Short 2006 only reported this outcome for the group
with active treatment. Only one study reported on long-term cure
(Leslie 2005). Eight studies reported on adverse effects, of which
one reported the rates but not the nature of the adverse effects (
Hanna 2006).
Topical treatments (Analyses 4 to 11)
Bazza reported on a study where treatments were randomised to
the right or left side of the body. Application of 5% potassium
hydroxide was compared to 0.9% saline. In both groups 17/20
patients were cured after 12 weeks. The same comparison was
made by Short 2006. Treatment with 10% potassium hydroxide
solution was successful after three months in 7/10 participants
(70%) compared with 2/10 (20%) in the saline group, which is
not statistically significant. Mild stinging was reported by most
participants and two participants developed post-inflammatory
pigmentary changes at the treatment site. In the treatment arm
two participants withdrew from the study due to discomfort of
the skin at the application site. Pooling these two studies resulted
in RR of 1.68 [0.36, 7.75], not significant) (Analysis 4.1).
Application of 10% povidone iodine solution and 50% salicylic
acid plaster (Ohkuma 1990) was effective in curing 20/20 participants (100%) compared with 3/5 (60%) who received povidone
iodine alone (RR 1.67, 95% CI 0.85 to 3.30, not significant) (
Analysis 5.1) and 7/10 (70%) who received salicylic plaster alone
(RR 1.43, 95% CI 0.95 to 2.16, not significant) (Analysis 6.1).
Thus, povidone iodine plus salicylic acid plaster resulted in more
participants being completely cured than with salicylic plaster or
povidone iodine alone, although this did not reach statistical significance. In addition, the mean time to cure was shorter for iodine plus salicylic acid plaster (mean time to cure of 26 days) than
for either iodine alone (mean time to cure of 86 days) or salicylic
plaster alone (mean time to cure of 47 days). Application of povidone iodine alone versus salicylic plaster alone resulted in a RR of
0.86 (95% CI 0.38 to 1.95, not significant) (Analysis 7.1).
All participants developed local redness of the skin at the treatment
site within three to seven days after the start of the treatment.
Duration was variable for each individual. The more marked the
inflammation, the earlier the participant was cured.
Treatment with 5% sodium nitrite co-applied daily with 5% salicylic acid under occlusion (Ormerod 1999) resulted in significantly more participants with complete resolution of the lesions
after three months: 12/16 (75%) compared with 3/14 (21%) participants in the control group, treated with an identical cream
but omitting sodium nitrite (RR 3.50, 95% CI 1.23 to 9.92; p =
0.02) (Analysis 8.1). This resulted in a number needed to treat of
10
less than two (i.e. for each cure achieved, two people need to be
treated). The mean number of treatment days was 38 (standard
deviation (SD) 20) in the treatment group and 49 (SD 25) in the
control group. Brown staining was reported in 6 of the 16 participants using the active treatment. Four out of 16 participants
(25%) stopped the active treatment because of irritation and lack
of efficacy. Two additional participants, who were cured, complained of significant irritation.
The results of the study by Hanna et al (Hanna 2006) could not
be included in the analysis, as the outcome (cure rate) was only
reported in number of visits, but not stating at what time these
visits took place.
Theos 2004 (see above for results after 4 weeks) also assessed cure
after 12 weeks. Application of 5% imiquimod cream resulted in
complete clearance in 4/12 patients versus 1/11 of the control
group who received vehicle cream (RR 3.67, 95% CI 0.48 to
28.00) (Analysis 2.3). Partial clearance was observed in 8/12 versus
2/11 patients (RR 3.67, 95% CI 0.98 to 13.67) (Analysis 2.4).
None of these differences were statistically significant.
Leslie 2005 was the only study assessing cure after a maximum of
6 months. Application of 10% phenol compared to 70% alcohol
resulted in 17/41 versus 16/36 cured patients (RR 0.93, 95% CI
0.56 to 1.56) (Analysis 9.1). Salicylic acid (12%) compared to 70%
alcohol resulted in 21/37 versus 16/36 cured patients (RR 1.28,
95% CI 0.81 to 2.02) (Analysis 10.1). None of these differences
were statistically significant.
Salicylic acid compared to phenol resulted in 21/37 versus 17/41
cured patients (RR=1.37, 95% CI 0.86 to 2.17, not significant) (
Analysis 11.1).
Systemic treatments (Analyses 12 and 13)
Treatment with systemic cimetidine 35 mg/kg/day (Antony 2001)
cleared lesions completely in 4/8 participants (50%) after four
months of treatment, compared with 5/11 (46%) given placebo
in the same period (Analysis 12.1); however, the difference for this
effect was not statistically significant (RR 1.10, 95% CI 0.43 to
2.84). No data were reported for the 50% (19/38) of participants
who withdrew from the study.
Treatment with calcarea carbonica (Manchanda 1997b) resulted
in improvement of 13/14 participants in the treatment arm and
1/6 in the placebo arm of the trial (RR 5.57, 95% CI 0.93 to
33.54, not significant) (Analysis 13.1). However, study duration,
time to resolution, and adverse events were not reported and the
study was not analysed by the intention-to-treat principle. The
number of dropouts (20/104 for the whole trial, including other
skin conditions) is unclear for the molluscum participants.
DISCUSSION
Summary of main results
Eleven studies, with a total number of 495 participants, examined
the effects of topical (9 studies), systemic, and homoeopathic interventions (1 study each). Limited evidence was found for the efficacy of the following comparisons of topical treatments: sodium
nitrite co-applied with salicylic acid compared to salicylic acid
alone; for Australian lemon myrtle oil compared to its vehicle,
olive oil; and for benzoyl peroxide compared to tretinoin. No statistically significant differences were found for 10 other comparisons.
Study limitations included no blinding (four studies), many
dropouts (three studies), and no intention-to-treat analysis; small
study sizes may have led to important differences being missed.
None of the evaluated treatment options were associated with serious adverse effects.
We did not include ’Summary of findings’ tables, because of the
large number of comparisons between treatments, and the small
number of studies per comparison (mostly one, and in one case,
two).
Although the update of our original review identified six new studies that could be included in our review, the overall conclusions
did not change, due to the small size of the studies and methodological shortcomings. No evidence either for or against the most
commonly used treatment options for molluscum contagiosum
was found.
The evidence identified by this systematic review is, therefore, insufficient to propose any one intervention for molluscum contagiosum. Additional well-designed, prospective, blinded randomised controlled studies on common treatment options for
molluscum contagiosum against a credible placebo or no intervention are needed to provide high-quality evidence upon which
to base clinical decision making.
Overall completeness and applicability of
evidence
No evidence either for or against the most commonly used treatment options for molluscum contagiosum was found. For example, we found only one study on curettage (Hanna 2006), but
the outcomes reported were not suitable for inclusion in this review. Only one study on cryotherapy (Caballero 1996) and one
on physical expression (squeezing) (Weller 1999) were identified.
Neither of these studies could be included in this review. There
is, therefore, an evidence gap regarding many promoted and used
treatment options for molluscum contagiosum. Furthermore, due
to the small sample sizes of the studies that were included and
which found no differences, clinically relevant differences might
be found if treatments were evaluated in larger samples. The cure
rates found by Weller for physical expression and for phenol ablation (75% and 77% of lesions respectively, after one month) (
Weller 1999) compare favourably to the 23% of children found
11
cured in the Japanese study on the natural history of the disease (
Takemura 1983). A newly included study (Leslie 2005) reported a
considerably lower cure rate for phenol and showed no difference
with 70% alcohol.
Several issues remain unclear due to lack of details in the published
papers. For example, it is unclear whether duration of treatment,
as used in Ormerod 1999, can be taken as a valid indicator for
time to cure given dropouts and other possible reasons for stopping treatment. Although Antony 2001 did not report on adverse
events, the 50% loss to follow-up rate in the trial might have been
caused by adverse effects of the treatment. It is unclear which dosing regimen was used in Manchanda 1997b when evaluating calcarea carbonica.
Several of the outcomes important to participants and clinicians
were not used as outcome measures in the studies we found. These
include recurrences, spread to other people, stigma, and quality of
life.
For only one comparison could we perform a meta-analysis (potassium hydroxide versus saline), this was however hampered by the
fact that one of the studies was a left-right comparison (Bazza) and
the other a ’normal’ parallel study (Short 2006).
We excluded studies on genital molluscum contagiosum and in
participants with lowered immunity. Our conclusions do not apply
to these participant groups as the need for treatment is probably
higher.
Quality of the evidence
All of the included studies were small in sample size with a median study size of 30 molluscum participants. The largest study
included 124 patients (Hanna 2006), but had as many as 4 treatment arms. Hence, all studies may have limited power, which was
reflected in the wide confidence intervals around the risk ratios.
In addition, many of the studies had large losses to follow-up, up
to 50% (Antony 2001).
Furthermore, in most of the included studies the control treatment used was not a placebo (Ohkuma 1990; Ormerod 1999;
Short 2006; Burke 2004; Saryazdi 2004; Theos 2004; Leslie 2005;
Hanna 2006). In these studies comparator treatment were, for example, olive oil, saline, and alcohol. These may have had some
potential treatment effect. Therefore, it was difficult to compare
the net effect of interventions given the absence of a placebo group
in most of the studies.
For only a small proportion of items in the ’Risk of bias’ table,
could a positive score be assigned (Figure 1). The lack of reported
details on several methodological issues and follow-up periods,
together with the small number of participants gives rise to doubts
about the validity of the results of some of the studies. We were not
able to assess publication bias in this review, e.g. by constructing
a funnel plot, due to the lack of directly comparable studies.
12
Figure 1. Risk of bias table: review authors’ judgements about each methodological quality item for each
included study.
13
Potential biases in the review process
Given the thoroughness of our searching efforts we do not expect
that we missed relevant randomised trials. One study is still ongoing (NCT00667225). Given the fact that seven of the included
studies were published recently (i.e. after 2000) we expect more
studies comparing treatments for molluscum contagiosum to be
published over the coming years.
We chose our primary outcome measure to be clinical cure after
one month, calculated from the last day of treatment. However,
this may not be the most appropriate outcome measure to cover
the variety of treatments for molluscum. For example, when comparing a method of physical destruction (e.g. curettage) with a
topical treatment that is applied during several days or weeks, our
primary outcome measure would probably favour the first type of
treatment. Another example is when treatment is continued until
resolution of all lesions (e.g. Ohkuma 1990). Although no clearcut solution seems available, and so far only one trial studied physical destruction (Hanna 2006), it is advisable to always consider
multiple outcome measures and also to take the burden of treatment into account.
Agreements and disagreements with other
studies or reviews
One other systematic review was found (Schmitt 2008). This review included six randomised trials, all of which were also included
in our review. The conclusions of this review are similar to ours.
Several of the interventions used for molluscum contagiosum have
also been applied in other skin disorders as well as in other diseases. Here we list some of these, as reported in recently published
Cochrane reviews. The effect of cryotherapy has been investigated
in randomised trials for several other conditions, with varying success. (Shelley 2007, Gibbs 2006, Bath-Hextall 2007) Salicylic acid
performed better than placebo in cutaneous warts (Gibbs 2006)
and in chronic plaque psoriasis (Mason 2009). Imiquimod showed
promising results in basal cell carcinoma (Bath-Hextall 2007), but
did not perform better than placebo in cutaneous leishmaniasis (
González 2008).
AUTHORS’ CONCLUSIONS
Implications for practice
No reliable evidence-based recommendations can be given for the
treatment of molluscum contagiosum at present. We were unable
to include outcomes of randomised controlled trials that addressed
physical destruction of molluscum lesions. Until robust evidence
emerges for effective and safe treatment, clinicians should consider
expectant management, i.e. awaiting spontaneous resolution of
the molluscum lesions.
Implications for research
(a) Additional well-designed, prospective, blinded randomised
controlled studies are needed to provide high quality clinical trial
evidence upon which to base clinical decision-making. Future
studies evaluating treatments for molluscum contagiosum should,
as a priority, focus on commonly promoted and commonly used
options for treatment (e.g. curettage and cryotherapy).
(b) Limited data on the natural history of molluscum contagiosum
is available. Additional studies into the rate of resolution without
active interventions are therefore needed, preferably assessing this
after various follow-up times (e.g. 1, 3, 6, and 12 months). This
will help guide decisions concerning the use of active treatments.
(c) Outcome measures of future trials should preferably include
recurrence rates, spread of the disease to other people, diseaserelated quality of life, and scarring.
(d) A standardised outcome measure (e.g. time to resolution of
the lesions or resolution after three months) would make studies
easier to compare.
(e) Statistical power must be considered in conjunction with outcomes that are meaningful for people with molluscum contagiosum. For example, it is likely that a treatment that results in statistically fewer lesions may not be considered worthwhile because this
reduction may not be sufficient to improve appearance or quality
of life. People should be enabled to weigh costs and benefits, taking
into account resolution of lesions, adverse effects, and treatment
burden.
(f ) Molluscum contagiosum is a common disease in immunocompromised people (e.g. people living with HIV). There is also a
sexually transmitted variant that affects immunocompetent sexually active people, which was excluded from this review. There
is a need for reviews of studies of treatments for these important
subgroups of people with molluscum contagiosum.
ACKNOWLEDGEMENTS
The authors thank Jack Menke, Sanjay Gajadin, and Marjolein
Tasche for their assistance when writing the first version of our
review. The authors would also like to thank Adrie Hollestein,
Daan Muris, Kazutomo Ohkuma, Tony Ormerod, Jane Sterling,
and Hywel Williams for drawing our attention to relevant studies.
Drs. Manchanda, Kazutomo Ohkuma, and Anthony Ormerod
kindly provided additional information regarding their studies,
and Kate Short and Mohammed Bazza generously sent us their
full paper before it was submitted for publication. The editorial
base provided help in tracing and translating papers. We also thank
Himiko Luiken for translating the unique study on the natural
history of molluscum contagiosum by Tsukasa Takemura and colleagues, and Taixiang Wu for interviewing Dr He on details of her
14
study design. We thank Alireza Firooz for assessing the paper by
Salmanpour and colleagues, and Susheera Chatpoedprai for providing additional information on their study.
The editorial base would like to thank the following people who
were external referees for this review: Anthony Ormerod and Paula
Beattie (content experts) and Jack Tweed (Consumer). They would
also like to thank Philippa Middleton (Methods Editor) and Jo
Leonardi-Bee (Statistical Editor) for their help with restructuring
the review and analysing the data.
We thank Finola Delamere, Philippa Middleton, Tina Leonard,
Jo Leonardi-Bee, Hywel Williams, Jack Gibson, Bob Dellavalle,
Alan Arbuckle, Anthony Ormerod, Paula Beatty, and Jack Tweed
for their comments on earlier drafts of the review.
For the update of this review the editorial base would like to thank
the Key Editor Bob Dellavalle with Alan Arbuckle, Jack Gibson
who acted as the statistical referee, Anthony Ormerod who was
the clinical content referee, and Jack Tweed the consumer referee.
REFERENCES
References to studies included in this review
Antony 2001 {published data only}
∗
Antony F, Cliff S, Ahmad A, Holden C. Double-blind placebocontrolled study of oral cimetidine treatment for molluscum
contagiosum (conference abstract). British Journal of Dermatology
2001;145 Suppl 59:126.
Bazza {unpublished data only}
∗
Bazza MA, Ryatt KS. Sterile normal 0.9% saline as a effective 5%
potassium hydroxide in treatment of molluscum contagiosum, and
safer. unpublished manuscript received May 2007.
Burke 2004 {published data only}
∗
Burke BE, Baillie J-E, Olson RD. Essential oil of Australian
lemon myrtle (Backhousia citriodora) in the treatment of
molluscum contagiosum in children. Biomedicine &
Pharmacotherapy 2004;58:245–7.
Hanna 2006 {published data only}
∗
Hanna D, Hatami A, Powell J, Marcoux D, Maari C, Savard P, et
al.A prospective randomized trial comparing the efficacy and
adverse effects of four recognized treatments of molluscum
contagiosum in children. Pediatric Dermatology 2006;23(6):574–9.
McCuaig CC, Hatami A, Powell J, Maari C, Marcoux D, Thibeault
H. Mollusca contagiosa: what treatment to use when? (conference
abstract). Journal of the European Academy of Dermatology &
Venereology 2005;19(Suppl 2):8.
Leslie 2005 {published data only}
∗
Leslie KS, Dootson G, Sterling J. Does treatment of molluscum
contagiosum affect clearance? [conference abstract of ongoing
study]. British Journal of Dermatology 2004;151(suppl 68):67.
∗
Leslie KS, Dootson G, Sterling JC. Topical salicylic acid gel as a
treatment for molluscum contagiosum in children. Journal of
Dermatological Treatment 2005;16(5-6):336–40.
Manchanda 1997b {published data only}
∗
Manchanda RK, Mehan N, Nahl R, Atey R. Double blind
placebo controlled clinical trials of homeopathic medicines in warts
and molluscum contagiosum. Central Council for Research in
Homeopathy Quarterly Bulletin 1997;19:25–9.
Ohkuma 1990 {published data only}
∗
Ohkuma M. Molluscum contagiosum treated with iodine
solution and salicylic acid plaster. International Journal of
Dermatology 1990;29(6):443–5.
Ormerod 1999 {published data only}
∗
Ormerod AD, White MI, Shah SA, Benjamin N. Molluscum
contagiosum effectively treated with a topical acidified nitrite, nitric
oxide liberating cream. British Journal of Dermatology 1999;141(6):
1051–3.
Saryazdi 2004 {published data only}
Saryazdi S. The comparative efficacy of benzoyl peroxide 10%
cream and tretinoin 0.05% cream in the treatment of molluscum
contagiosum. Abstract 10th World Congress on Pediatric
Dermatology. Pediatric Dermatology 2004;21(3):399.
Short 2006 {published and unpublished data}
Short KA, Fuller LC, Higgins EM. Double-blind, randomised,
placebo-controlled trial of the use of topical 10% potassium
hydroxide solution of molluscum contagiosum. Unpublished
manuscript.
∗
Short KA, Fuller LC, Higgins EM. Double-blind, randomized,
placebo-controlled trial of the use of topical 10% potassium
hydroxide solution in the treatment of molluscum contagiosum.
Pediatric Dermatology 2006;23:279–81.
Short KA, Fuller LC, Higgins EM. Double-blind randomized
placebo-controlled trial of the use of topical potassium hydroxide in
the treatment of molluscum contagiosum. British Journal of
Dermatology 2002;147 Suppl 62:95 (abstract).
15
Theos 2004 {published data only}
∗
Theos AU, Cummins R, Silverberg NB, Paller AS. Effectiveness
of imiquimod cream 5% for treating childhood molluscum
contagiosum in a double-blind, randomized pilot trial. Cutis 2004;
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molluscum contagiosum in males with an analog of imiquimod 1%
in cream: a placebo-controlled, double-blind study. Journal of
Dermatology 1998;25(5):309–13.
References to studies excluded from this review
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treatment for molluscum contagiosum: a double-blind, placebocontrolled study. Journal of the Philippine Dermatological Society
2003;12(1):28–35.
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NCT00667225. Efficacy of cantharidin in molluscum
contagiosum. ClinicalTrials.Gov/ct2/show/NCT00667225
(accessed 18 February 2009).
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∗
Indicates the major publication for the study
19
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]
Antony 2001
Methods
Double-blind randomised placebo-controlled trial. Method of generation of randomisation sequence is unclear, as is concealment of allocation. No intention-to-treat analysis.
UK, Department (Dept) of Dermatology
Participants
38 patients (1 to 16 years, M/F 18/20) were enrolled, for 19 patients complete data were
obtained, 8 of which had been randomised into the treatment arm. 19 patients withdrew
from the study, no data on reasons for withdrawal
Interventions
35 mg/kg/day cimetidine, given once daily as oral suspension versus a matching placebo
Outcomes
Complete clearance after 4 months treatment. Reduction of lesions. Adverse events: not
mentioned
Notes
50% dropout rate. Published abstract only
Risk of bias
Item
Authors’ judgement
Description
Adequate sequence generation?
Unclear
Quote: “Randomized”. No details in abstract
Allocation concealment?
Unclear
Method of concealment is not described in
the abstract
Blinding?
All outcomes
Yes
Quote:
“Double-blind
placebocontrolled”; “The dose of cimetidine was
35 mg/kg−1 /day −1 ”; “The placebo group
received a manufactured placebo”. Probably done, placebo-controlled, both suspensions
Incomplete outcome data addressed?
Short-term outcomes (1 month)
Unclear
Not reported in the abstract
No
Medium and long-term outcomes (3 and 6
months)
4 months: 19/35 completed the treatment
course. Quote: “The number of patients
who received placebo or cimetidine was
similar in the groups that did not attend or
withdrew.” > 30% withdrawals
Free of selective reporting?
Unclear
Unclear
20
Antony 2001
(Continued)
Free of other bias?
Unclear
Quote: “The mean age and sex of the
patients and incidence of atopic disease
in each treatment group was similar.” No
compliance data
Bazza
Methods
Randomised controlled trial. Body sides were randomised left-right. UK, Dept of Dermatology
Participants
30 children (2 to 12 years of age, M/F 18/12) were recruited
Interventions
Sterile normal 0.9% saline versus 5% potassium hydroxide
Outcomes
Complete clearance of lesions; side-effects
Notes
Unpublished, year of study unclear. Unpublished paper obtained in 2007
Risk of bias
Item
Description
Unclear
Quote: “Where treatment with 0.9% NS
and 5% KOH solution was randomized to
right or left side of body”. Insufficient information
Unclear
Quote: “Where treatment with 0.9% NS
and 5% KOH solution was randomized to
right or left side of body”. Insufficient information
Blinding?
All outcomes
Yes
Quote: “30 patients were recruited in this
double-blind study”. “All subjects were
given seven bottles clearly labelled R and
seven bottles labelled L, for use on the right
and left side of the body respectively (patient and investigator did not know which
is active site)”
Unclear
Unknown when patients dropped out, no
short-term outcomes provided
No
months)
12 weeks: 10/30 did not complete study,
2 withdrew due to severe stinging from
KOH, and 8 children were lost to followup. > 30% drop-outs
21
Bazza
(Continued)
Unclear
Unclear
Free of other bias?
Unclear
No baseline comparison. No compliance
data
Burke 2004
Methods
Randomised controlled trial, USA, outpatient clinic
Participants
31 children, mean age 4.6 years. Sex not reported
Interventions
10% lemon myrtle oil or vehicle (olive oil)
Outcomes
Complete clearance or > 90% reduction in number of lesions
Notes
-
Risk of bias
Item
Description
Yes
Quote: “Children were randomized to active treatment or vehicle (virgin olive oil) by
blindly choosing a token numbered from
1 to 100. Odd numbers were assigned to
active treatment even numbers to vehicle”
Yes
Quote: “Children were randomized to active treatment or vehicle (virgin olive oil) by
blindly choosing a token numbered from
1 to 100.” “Parents and physicians were
blinded to treatment protocol. A treatment
key was held by a participating pharmacist
(no patient contact) until study completion”
Blinding?
All outcomes
Yes
Quote: “Parents and physicians were
blinded to treatment protocol. A treatment
key was held by a participating pharmacist
(no patient contact) until study completion.” “A mild synthetic lemon fragrance
not containing citral was added to scent the
control olive oil preparation.This fragrance
by itself had no therapeutic effect.” Vehicle
controlled
22
Burke 2004
(Continued)
Yes
21 days: 4/31 withdrew: 1/16 in lemon
myrtle oil group lost to follow-up; 3/15
missing in vehicle group, withdrew because
of worsening of the molluscum. Withdrawn patients included in analysis as failures
Unclear
months)
The study did not address medium and
long-term outcomes
Unclear
Unclear
Free of other bias?
Unclear
The mean number of lesions at enrolment
did not differ between treatment groups.
No sex or age comparison between groups.
No compliance data
Hanna 2006
Methods
Randomised controlled trial, Canada, Montreal, Dermatology clinic
Participants
124 children, 1 to 16 years of age
M/F 57/67
Interventions
Four arms: curettage; topical cantharidin 0.7%; topical salicylic acid 16.7% + lactic acid
16.7%; topical imiquimod cream 5%
Outcomes
Number of visits required. Intervals between study visits not reported, so outcome data
not suitable for inclusion
Notes
Total number of patients unclear. Percentage of group 3 in table 1 does not correspond
to number mentioned in text
Risk of bias
Item
Description
Yes
Quote: “The randomization list was generated by specialized computer software (PCPLAN, Dalal, 1996)”
Unclear
Quote: “The randomization list was generated by specialized computer software (PCPLAN, Dalal, 1996).” Insufficient information
23
Hanna 2006
(Continued)
Blinding?
All outcomes
No
Quote: “This is not a double-blind study.”
Physical versus topical treatment
Unclear
Not reported
Unclear
months)
Not reported
Unclear
Unclear
Free of other bias?
Unclear
data
Leslie 2005
Methods
Randomised controlled trial. UK, outpatient departments of teaching hospital and district general hospital
Participants
114 children, 1 to 15 years of age, sex not reported
Interventions
Topical salicylic acid 12%, or phenol 10% with 70% alcohol, or 70% alcohol
Outcomes
Complete clearance of lesions
Notes
-
Risk of bias
Item
Description
Yes
Quote: “The participants were randomized
according to a random number table”
No
Quote: “The investigators were not blinded
to randomization”
Blinding?
All outcomes
No
Quote: “The patients in the salicylic acid
groups were aware of their treatments. The
other two groups treated with vehicle or
phenol were single-blinded, as the patients/
parents were unaware of which treatment
they received.” “The vehicle and diluted
phenol were prepared by the hospital pharmacy and labelled with a letter”
24
Leslie 2005
(Continued)
Unclear
Up to 6 months: 31/114 lost to follow-up:
13/37 in salicylic acid arm, 9/41 in dilute
phenol arm, 9/36 in alcohol arm
No
months)
Up to 6 months: 31/114 lost to follow-up:
13/37 in salicylic acid arm, 9/41 in dilute
phenol arm, 9/36 in alcohol arm. > 30%
drop-outs
Unclear
Unclear
Free of other bias?
Unclear
Quote: “The baseline characteristics of the
three groups were similar.” See also Table
I, Baseline characteristics. No compliance
data
Manchanda 1997b
Methods
Double-blind randomised controlled trial, addressing various types of warts (n = 124),
including molluscum contagiosum (n = 20). India, Homoeopathic Medical College &
Hospital, New Delhi. Randomisation sequence was generated manually, identity of the
drugs was kept secret in a sealed cover (personal communication with Dr Manchanda).
No intention-to-treat analysis
Participants
14 molluscum patients (age and sex unknown) randomised into the treatment arm, 6
patients were randomised to receive plain sugar globules as a placebo (personal communication Dr Manchanda). 10 patients were aged below 10 years, 7 from 10 to 20 and 3
were from the age group 21 to 30 years (personal communication with Dr Manchanda)
Interventions
Different potencies of a homeopathic drug called calcarea carbonica daily for 15 days (n
= 14) versus sugar globules (placebo). Unclear which patients received what potency
Outcomes
Improvement (not clear after what period)
Notes
Paper reports on (1) cross-over study (2) parallel study. The cross-over study was excluded,
because less than 5 patients in one of the arms
Risk of bias
Item
Description
Unclear
Quote: ”In this research design, each case
was initially given a drug code in 30 potency which could be either active drug or
placebo.“ Randomisation not mentioned
in paper, ”sequence was generated manually“ (personal communication)
25
Manchanda 1997b
(Continued)
Unclear
Quote: ”In this research design, each case
was initially given a drug code in 30 potency which could be either active drug or
placebo.“ ”Therefore it was found that after decoding method of concealment is not
described“
Blinding?
All outcomes
Yes
Quote: ”Two types of placebo controlled
double-blind clinical trials were undertaken.“ ”The subjects were given both drug
and placebo.“ Quote (personal communication): “The identity of the drugs was kept
secret in a sealed cover which was opened
only at the time un-blinding the experiment.” “The plain sugar globules looks like
homoeopathic drug Calcerea carbonica was
used as placebo.” Probably done
Yes
15 days: 20/124 dropouts, unclear what
skin disease and group assignment
No
months)
Only 15 days
Unclear
Unclear
Free of other bias?
Unclear
data
Ohkuma 1990
Methods
Randomised controlled trial (written correspondence Dr Ohkuma), the method of generation of randomisation sequence remained unclear, as was the concealment of allocation. It was also unclear if participants were analysed according to the group to which
they were randomised (intention-to treat analysis) and how blinding was performed.
Japan, Department of Dermatology
Participants
35 patients with molluscum contagiosum, aged between 2 and 9 years (M/F 21/14)
Interventions
3 interventions were compared: 10% povidone iodine solution combined with 50%
salicylic acid plaster (n = 20), iodine alone (n = 5) and salicylic plaster alone (n = 10)
Outcomes
Time to cure
Adverse events
Study duration unknown
Notes
-
26
Ohkuma 1990
(Continued)
Risk of bias
Item
Description
Unclear
Randomised (personal communication,
not in paper). Insufficient information
about the sequence generation
Unclear
Insufficient information about the sequence generation
Blinding?
All outcomes
No
Probably not, iodine versus salicylic plaster:
hard to mask
Unclear
No loss reported, all patients in outcome
table. Follow-up period unclear. Duration
of treatment varied from 7 to 64 days
Unclear
months)
No loss reported, all patients in outcome
table. Follow-up period unclear. Duration
of treatment varied from 7 to 64 days
Unclear
Unclear
Free of other bias?
Unclear
Quote: “In the former, two girls and three
boys between the age of 3 and 5 were included and 4 girls and 6 boys between 2
and 9 comprised the latter control group.”
No imbalance for sex. No compliance data
Ormerod 1999
Methods
Group sequential double-blind randomised trial. All participants were analysed according
to group assignment (intention-to-treat). Two patients did not complete the trial. UK,
Department of Dermatology
Participants
30 molluscum patients were enrolled, with 16 in the acidified nitrite group and 14
controls, with a median age of 6 years, 22 girls and 8 boys. Exclusion criteria were age
below 1 year of age, pregnant or lactating women, and taking immunosuppressive drugs
or known to have HIV infection
Interventions
5% sodium nitrite co-applied daily with 5% salicylic acid under occlusion versus identical
cream with 5% salicylic acid omitting sodium nitrite
Outcomes
Time to complete resolution
Adverse events
Study duration 3 months
27
Ormerod 1999
(Continued)
Notes
-
Risk of bias
Item
Description
Unclear
Quote: “Group sequential design in which
subjects were randomized to receive either”. Insufficient information about the
sequence generation
Unclear
Method of concealment not described
Blinding?
All outcomes
No
Quote: “Double-blind, group sequential
design in which subjects were randomized
to receive either 5% sodium nitrite co-applied with 5% salicylic acid under occlusion, or identical cream with 5% salicylic
acid but omitting sodium nitrite, as a control.” Not done, active intervention was associated with brown staining
Unclear
Only long-term data
No
months)
21/30 dropouts after 3 months
Unclear
Unclear
Free of other bias?
Unclear
No compliance data. Duration and number of lesions were very similar (communication with author)
Saryazdi 2004
Methods
Randomised trial, Iran, hospital dermatology clinic
Outcomes given for 23 patients of 30 randomised, original distribution unknown, assumed 15:15
Participants
30 children, age and sex unknown
Interventions
Topical benzoyl peroxide 10% cream versus tretinoin 0.05% cream, 2 times daily (TD)
for 4 weeks
Outcomes
Count of lesions, lesion free after 6 weeks
Side-effects limited to mild dermatitis in both groups
28
Saryazdi 2004
(Continued)
Notes
Information based on abstract, proportions cured used for estimating absolute numbers.
Abstract published in 2004 - unclear when study was carried out
Risk of bias
Item
Description
Unclear
Not reported
Unclear
Not reported
Blinding?
All outcomes
Unclear
“Investigator masked”
Unclear
Not reported
Unclear
months)
Not reported
Unclear
Unclear
Free of other bias?
Unclear
No baseline characteristics nor compliance
data
Short 2006
Methods
Double-blind randomised placebo controlled trial. UK, Department of Dermatology,
London. The method of generation of the randomisation sequence is unclear as is concealment of allocation. All participants were analysed according to group assignment (
intention-to-treat analysis). 19/20 completed the study.
Participants
20 children from a paediatric dermatology clinic, age range 2 to 12 years, M/F 6/14.
Exclusion criteria were known immunodeficiency and facial lesions
Interventions
Application of 10% potassium hydroxide solution twice daily applied with a cotton
swab, continued until the lesions showed signs of inflammation (n = 10). The control
group received saline (n = 10)
Outcomes
Time to resolution
Adverse events
Study duration 3 months
Notes
Number of patients who completed the study differs between unpublished paper (18/20)
and published paper (19/20). Latter number included in corrected version of 2009
update (December 2009).
29
Short 2006
(Continued)
Risk of bias
Item
Description
Unclear
Quote: “The children were randomly allocated by the dispensing pharmacist to receive one of two treatments”. Insufficient
information.
Unclear
Quote: “The children were randomly allocated by the dispensing pharmacist to receive one of two treatments.” Central allocation: Pharmacy-controlled
Blinding?
All outcomes
Yes
Quote: “Both the patients and the observer
were blinded”. “Both solutions were dispensed in identical, unlabeled bottles. The
sequence was not revealed until the end of
the study.” Staining and stinging reported
in the KOH group. Patient, care provider,
and outcome assessor probably blinded
Yes
2 weeks: 1/20 not completed the study;
1/10 in the KOH group withdrew after 2
weeks because of discomfort of the skin localised to the application site
Yes
months)
90 days: 1/20 not completed the study;
1/10 in the KOH group withdrew after 2
weeks because of discomfort of the skin localised to the application site
Unclear
Unclear
Free of other bias?
Unclear
No baseline imbalance for sex, lesion site,
and numbers. No compliance data
Theos 2004
Methods
Randomised controlled trial. USA, Alabama, Illinois, New York
Participants
23 children, 1 to 9 years of age, M/F 12/11
Interventions
Imiquimod cream 5% or vehicle
Outcomes
Complete or partial clearance (> 30% decrease from baseline lesion count)
30
Theos 2004
(Continued)
Notes
-
Risk of bias
Item
Description
Unclear
Quote: “Eligible patients were randomized
to either imiquimod or vehicle”. Insufficient information
Unclear
Quote: “Eligible patients were randomized
to either imiquimod or vehicle”. Insufficient information
Blinding?
All outcomes
Yes
Quote: “In a Double Blind, Randomized
Pilot Trial”; “imiquimod vs vehicle”. Only
patients and physicians involved
Yes
2 weeks: 2/23 not completed the study (
discontinued treatment)
Yes
months)
2 weeks: 2/23 not completed the study (
discontinued treatment)
Unclear
Unclear
Free of other bias?
Unclear
Baseline imbalance for mean lesion count,
imiquimod: 27.0 versus vehicle: 19.4 (not
statistically significant). No compliance
data
KOH = Potassium Hydroxide
NS = Normal Saline
Characteristics of excluded studies [ordered by study ID]
Barton 2002
HIV-infected patients (n = 40)
Caballero 1996
RCT comparing 2 types of cryotherapy for cutaneous skin lesions: 124 patients, among which 10 molluscum
patients, distributed 9:1 over 2 arms
Chatproedrai 2007
Not randomised (personal communication)
31
(Continued)
de Waard 1990
Study on analgesic effect of lidocaine/prilocaine (EMLA) cream before physical therapy. Not a focus of this
review (n = 83)
He 2001
Large parallel controlled study (n = 1656), with 4 arms, no randomisation (personal communication with
Dr He through Taixiang Wu)
Juhlin 1980
review (n = 24)
Manchanda 1997a
Cross-over study with different types of warts (n = 43), 10 molluscum patients. 1 of the treatment arms
(placebo first?) had less than 2 patients
Rosendahl 1988
review (n = 55)
Salmanpour 2006
Not randomised but alternate assignment (personal communication, Alireza Firooz)
Syed 1994
RCT, n = 150, mainly genital lesions, which is not a focus of this review
Syed 1998
RCT, n = 100, mainly genital lesions, which is not a focus of this review
Weller 1999
Controlled trial (n = 16), comparing phenol ablation and physical expression. Lesions were unit of treatment
and analysis. No randomisation
Yabut-Catalasan 2003
Controlled trial, N=34, aged 2 to 12 years. 10% potassium hydroxide versus placebo. Not randomised, but
alternate assignment
32
Characteristics of ongoing studies [ordered by study ID]
NCT00667225
Trial name or title
Efficacy of cantharidin in molluscum contagiosum: a randomised, blinded, placebo-controlled prospective
study
Methods
Randomized, double-blind (subject, caregiver, investigator, outcomes assessor)
Participants
Molluscum patients
Interventions
Topical cantharidin 0.7%
Vehicle
Outcomes
Complete and partial clearance after 8 weeks or 5 visits
Starting date
January 2008
Contact information
jacquelyn.coloe@osumc.edu
Notes
-
33
DATA AND ANALYSES
Comparison 1. Topical: 10% Australian lemon myrtle oil vs. vehicle (olive oil)
Outcome or subgroup title
1 Complete clearance or > 90%
reduction after 3 weeks
No. of
studies
No. of
participants
1
31
Statistical method
Risk Ratio (M-H, Fixed, 95% CI)
Effect size
17.88 [1.13, 282.72]
Comparison 2. Topical: 5% imiquimod vs. vehicle
1 Complete clearance after 4 weeks
2 Partial clearance after 4 weeks
3 Complete clearance after 12
weeks
4 Partial clearance after 12 weeks
No. of
studies
No. of
participants
1
1
1
23
23
23
4.62 [0.25, 86.72]
13.85 [0.88, 217.26]
3.67 [0.48, 28.00]
1
23
3.67 [0.98, 13.67]
Statistical method
Effect size
Comparison 3. Topical: 10% benzoyl peroxide cream vs. 0.05% tretinoin cream (ITT)
No. of
studies
No. of
participants
1 Free of lesions after 6 weeks
1
30
Statistical method
Effect size
2.2 [1.01, 4.79]
Comparison 4. Topical: 10% KOH vs. saline
1 Clinical cure at medium-term
follow-up (3 months)
No. of
studies
No. of
participants
2
60
Statistical method
Risk Ratio (M-H, Random, 95% CI)
Effect size
1.68 [0.36, 7.75]
34
Comparison 5. Topical: 10% povidone iodine and 50% salicylic plaster vs. 10% povidone iodine alone
1 Clinical cure at end of study
(duration unknown)
No. of
studies
No. of
participants
1
25
Statistical method
Effect size
1.67 [0.85, 3.30]
Comparison 6. Topical: 10% povidone iodine and 50% salicylic acid plaster vs. 50% salicylic plaster alone
(duration unknown)
No. of
studies
No. of
participants
1
30
Statistical method
Effect size
1.43 [0.95, 2.16]
Comparison 7. Topical: 10% povidone iodine vs. 50% salicylic acid plaster
(duration unknown)
No. of
studies
No. of
participants
1
15
Statistical method
Effect size
0.86 [0.38, 1.95]
Comparison 8. Topical: 5% sodium nitrite in 5% salicylic acid vs. 5% salicylic acid alone
No. of
studies
No. of
participants
1
30
Statistical method
Effect size
3.5 [1.23, 9.92]
35
Comparison 9. Topical: 10% phenol/70% alcohol vs. 70% alcohol (ITT)
1 Complete clearance at end of
study (max 6 months)
No. of
studies
No. of
participants
1
77
Statistical method
Effect size
0.93 [0.56, 1.56]
Comparison 10. Topical: 12% salicylic acid vs. 70% alcohol (ITT)
study (6 months max)
No. of
studies
No. of
participants
1
73
Statistical method
Effect size
1.28 [0.81, 2.02]
Comparison 11. Topical: 12% salicylic acid vs. 10% phenol/70% alcohol (ITT)
study (max 6 months)
No. of
studies
No. of
participants
1
78
Statistical method
Effect size
1.37 [0.86, 2.17]
Comparison 12. Systemic: cimetidine vs. placebo
No. of
studies
No. of
participants
1
19
Statistical method
Effect size
1.1 [0.43, 2.84]
36
Comparison 13. Systemic: calcarea carbonica vs. placebo
1 Improvement at end of study
(duration unknown)
No. of
studies
No. of
participants
1
20
Statistical method
Effect size
5.57 [0.93, 33.54]
Analysis 1.1. Comparison 1 Topical: 10% Australian lemon myrtle oil vs. vehicle (olive oil), Outcome 1
Complete clearance or > 90% reduction after 3 weeks.
Review:
Comparison: 1 Topical: 10% Australian lemon myrtle oil vs. vehicle (olive oil)
Outcome: 1 Complete clearance or > 90% reduction after 3 weeks
Study or subgroup
Favours lemon tree oil
Favours vehicle
n/N
n/N
9/16
0/15
100.0 %
17.88 [ 1.13, 282.72 ]
16
15
100.0 %
17.88 [ 1.13, 282.72 ]
Burke 2004
Total (95% CI)
Risk Ratio
Weight
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI
Total events: 9 (Favours lemon tree oil), 0 (Favours vehicle)
Heterogeneity: not applicable
Test for overall effect: Z = 2.05 (P = 0.041)
0.01
0.1
Favours vehicle
1
10
100
Favours lemon tree oil
37
Analysis 2.1. Comparison 2 Topical: 5% imiquimod vs. vehicle, Outcome 1 Complete clearance after 4
weeks.
Review:
Comparison: 2 Topical: 5% imiquimod vs. vehicle
Outcome: 1 Complete clearance after 4 weeks
Study or subgroup
Favours imiquimod
Favours vehicle
n/N
n/N
2/12
0/11
100.0 %
4.62 [ 0.25, 86.72 ]
12
11
100.0 %
4.62 [ 0.25, 86.72 ]
Theos 2004
Total (95% CI)
Risk Ratio
Weight
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI
Total events: 2 (Favours imiquimod), 0 (Favours vehicle)
0.01
0.1
1
10
Favours vehicle
100
Favours imiquimod
Analysis 2.2. Comparison 2 Topical: 5% imiquimod vs. vehicle, Outcome 2 Partial clearance after 4 weeks.
Review:
Outcome: 2 Partial clearance after 4 weeks
Study or subgroup
Favours imiquimod
Favours vehicle
n/N
n/N
7/12
0/11
100.0 %
13.85 [ 0.88, 217.26 ]
12
11
100.0 %
13.85 [ 0.88, 217.26 ]
Theos 2004
Total (95% CI)
Risk Ratio
Weight
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI
0.01
0.1
Favours vehicle
1
10
100
Favours imiquimod
38
Analysis 2.3. Comparison 2 Topical: 5% imiquimod vs. vehicle, Outcome 3 Complete clearance after 12
weeks.
Review:
Outcome: 3 Complete clearance after 12 weeks
Study or subgroup
Favours imiqumod
Favours vehicle
n/N
n/N
4/12
1/11
100.0 %
3.67 [ 0.48, 28.00 ]
12
11
100.0 %
3.67 [ 0.48, 28.00 ]
Theos 2004
Total (95% CI)
Risk Ratio
Weight
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI
Total events: 4 (Favours imiqumod), 1 (Favours vehicle)
0.01
0.1
1
Favours vehicle
10
100
Favours imiquimod
Analysis 2.4. Comparison 2 Topical: 5% imiquimod vs. vehicle, Outcome 4 Partial clearance after 12 weeks.
Review:
Outcome: 4 Partial clearance after 12 weeks
Study or subgroup
Favours imiquimod
Favours vehicle
n/N
n/N
8/12
2/11
100.0 %
3.67 [ 0.98, 13.67 ]
12
11
100.0 %
3.67 [ 0.98, 13.67 ]
Theos 2004
Total (95% CI)
Risk Ratio
Weight
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI
0.01
0.1
1
Favours vehicle
10
100
Favours imiquimod
39
Analysis 3.1. Comparison 3 Topical: 10% benzoyl peroxide cream vs. 0.05% tretinoin cream (ITT), Outcome
1 Free of lesions after 6 weeks.
Review:
Comparison: 3 Topical: 10% benzoyl peroxide cream vs. 0.05% tretinoin cream (ITT)
Outcome: 1 Free of lesions after 6 weeks
Study or subgroup
benzoyl peroxide
tretinoin
n/N
n/N
11/15
5/15
100.0 %
2.20 [ 1.01, 4.79 ]
15
15
100.0 %
2.20 [ 1.01, 4.79 ]
Saryazdi 2004
Total (95% CI)
Risk Ratio
Weight
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI
Total events: 11 (benzoyl peroxide), 5 (tretinoin)
0.01
0.1
1
Favours tretinoin
10
100
Favours benzoyl peroxide
Analysis 4.1. Comparison 4 Topical: 10% KOH vs. saline, Outcome 1 Clinical cure at medium-term followup (3 months).
Review:
Comparison: 4 Topical: 10% KOH vs. saline
Outcome: 1 Clinical cure at medium-term follow-up (3 months)
Study or subgroup
Bazza
Short 2006
Total (95% CI)
10% KOH
saline
n/N
n/N
Risk Ratio
Weight
17/20
17/20
58.5 %
1.00 [ 0.77, 1.30 ]
7/10
2/10
41.5 %
3.50 [ 0.95, 12.90 ]
30
30
100.0 %
1.68 [ 0.36, 7.75 ]
M-H,Random,95% CI
Risk Ratio
M-H,Random,95% CI
Total events: 24 (10% KOH), 19 (saline)
Heterogeneity: Tau2 = 1.02; Chi2 = 5.44, df = 1 (P = 0.02); I2 =82%
0.1 0.2
0.5
Favours saline
1
2
5
10
Favours KOH
40
Analysis 5.1. Comparison 5 Topical: 10% povidone iodine and 50% salicylic plaster vs. 10% povidone iodine
alone, Outcome 1 Clinical cure at end of study (duration unknown).
Review:
Comparison: 5 Topical: 10% povidone iodine and 50% salicylic plaster vs. 10% povidone iodine alone
Outcome: 1 Clinical cure at end of study (duration unknown)
Study or subgroup
Povid Iodine + Salic
Povid Iodine
n/N
n/N
20/20
3/5
100.0 %
1.67 [ 0.85, 3.30 ]
20
5
100.0 %
1.67 [ 0.85, 3.30 ]
Ohkuma 1990
Total (95% CI)
Risk Ratio
Weight
M-H,Random,95% CI
Risk Ratio
M-H,Random,95% CI
Total events: 20 (Povid Iodine + Salic), 3 (Povid Iodine)
0.001 0.01 0.1
1
Favours iodine
10 100 1000
Favours iodine + sal
Analysis 6.1. Comparison 6 Topical: 10% povidone iodine and 50% salicylic acid plaster vs. 50% salicylic
plaster alone, Outcome 1 Clinical cure at end of study (duration unknown).
Review:
Comparison: 6 Topical: 10% povidone iodine and 50% salicylic acid plaster vs. 50% salicylic plaster alone
Study or subgroup
Ohkuma 1990
Total (95% CI)
Iodine + Salicylic
Salicylic alone
n/N
n/N
Risk Ratio
Weight
20/20
7/10
100.0 %
1.43 [ 0.95, 2.16 ]
20
10
100.0 %
1.43 [ 0.95, 2.16 ]
M-H,Random,95% CI
Risk Ratio
M-H,Random,95% CI
Total events: 20 (Iodine + Salicylic), 7 (Salicylic alone)
0.5
0.7
1
Favours salicyl
1.5
2
Favours iodine + sal
41
Analysis 7.1. Comparison 7 Topical: 10% povidone iodine vs. 50% salicylic acid plaster, Outcome 1 Clinical
cure at end of study (duration unknown).
Review:
Comparison: 7 Topical: 10% povidone iodine vs. 50% salicylic acid plaster
Study or subgroup
Povidone Iodine
Salicylic acid plast
n/N
n/N
Risk Ratio
Weight
Ohkuma 1990
3/5
7/10
100.0 %
0.86 [ 0.38, 1.95 ]
Total (95% CI)
5
10
100.0 %
0.86 [ 0.38, 1.95 ]
M-H,Random,95% CI
Risk Ratio
M-H,Random,95% CI
Total events: 3 (Povidone Iodine), 7 (Salicylic acid plast)
0.2
0.5
1
2
Favours sal plast
5
Favours iodine
Analysis 8.1. Comparison 8 Topical: 5% sodium nitrite in 5% salicylic acid vs. 5% salicylic acid alone,
Outcome 1 Clinical cure at medium-term follow-up (3 months).
Review:
Comparison: 8 Topical: 5% sodium nitrite in 5% salicylic acid vs. 5% salicylic acid alone
Study or subgroup
Ormerod 1999
Total (95% CI)
Acidified nitrite
Salicylic acid alone
n/N
n/N
Risk Ratio
Weight
12/16
3/14
100.0 %
3.50 [ 1.23, 9.92 ]
16
14
100.0 %
3.50 [ 1.23, 9.92 ]
M-H,Random,95% CI
Risk Ratio
M-H,Random,95% CI
Total events: 12 (Acidified nitrite), 3 (Salicylic acid alone)
0.1 0.2
0.5
Favours salicyl
1
2
5
10
Favours acid nitrite
42
Analysis 9.1. Comparison 9 Topical: 10% phenol/70% alcohol vs. 70% alcohol (ITT), Outcome 1 Complete
clearance at end of study (max 6 months).
Review:
Comparison: 9 Topical: 10% phenol/70% alcohol vs. 70% alcohol (ITT)
Outcome: 1 Complete clearance at end of study (max 6 months)
Study or subgroup
Favours phenol/alcohol
Favours alcohol
n/N
n/N
17/41
16/36
100.0 %
0.93 [ 0.56, 1.56 ]
41
36
100.0 %
0.93 [ 0.56, 1.56 ]
Leslie 2005
Total (95% CI)
Risk Ratio
Weight
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI
Total events: 17 (Favours phenol/alcohol), 16 (Favours alcohol)
0.01
0.1
1
Favours phenol/alcohol
10
100
Favours alcohol
Analysis 10.1. Comparison 10 Topical: 12% salicylic acid vs. 70% alcohol (ITT), Outcome 1 Complete
clearance at end of study (6 months max).
Review:
Comparison: 10 Topical: 12% salicylic acid vs. 70% alcohol (ITT)
Outcome: 1 Complete clearance at end of study (6 months max)
Study or subgroup
Favours salicylic acid
Favours alcohol
n/N
n/N
21/37
16/36
100.0 %
1.28 [ 0.81, 2.02 ]
37
36
100.0 %
1.28 [ 0.81, 2.02 ]
Leslie 2005
Total (95% CI)
Risk Ratio
Weight
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI
Total events: 21 (Favours salicylic acid), 16 (Favours alcohol)
0.01
0.1
1
10
100
Favours alcohol
43
Analysis 11.1. Comparison 11 Topical: 12% salicylic acid vs. 10% phenol/70% alcohol (ITT), Outcome 1
Complete clearance at end of study (max 6 months).
Review:
Comparison: 11 Topical: 12% salicylic acid vs. 10% phenol/70% alcohol (ITT)
Outcome: 1 Complete clearance at end of study (max 6 months)
Study or subgroup
Favours phenol
n/N
n/N
21/37
17/41
100.0 %
1.37 [ 0.86, 2.17 ]
37
41
100.0 %
1.37 [ 0.86, 2.17 ]
Leslie 2005
Total (95% CI)
Risk Ratio
Weight
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI
Total events: 21 (Favours salicylic acid), 17 (Favours phenol)
0.01
0.1
1
Favours salicylic
10
100
Favours phenol
Analysis 12.1. Comparison 12 Systemic: cimetidine vs. placebo, Outcome 1 Clinical cure at medium-term
follow-up (4 months).
Review:
Comparison: 12 Systemic: cimetidine vs. placebo
Study or subgroup
Cimetidine
Placebo
n/N
n/N
Risk Ratio
Weight
Antony 2001
4/8
5/11
100.0 %
1.10 [ 0.43, 2.84 ]
Total (95% CI)
8
11
100.0 %
1.10 [ 0.43, 2.84 ]
M-H,Random,95% CI
Risk Ratio
M-H,Random,95% CI
Total events: 4 (Cimetidine), 5 (Placebo)
0.2
0.5
Favours placebo
1
2
5
Favours cimetidine
44
Analysis 13.1. Comparison 13 Systemic: calcarea carbonica vs. placebo, Outcome 1 Improvement at end of
study (duration unknown).
Review:
Comparison: 13 Systemic: calcarea carbonica vs. placebo
Outcome: 1 Improvement at end of study (duration unknown)
Study or subgroup
Calcium Carbonicum
Placebo
n/N
n/N
13/14
1/6
100.0 %
5.57 [ 0.93, 33.54 ]
14
6
100.0 %
5.57 [ 0.93, 33.54 ]
Manchanda 1997b
Total (95% CI)
Risk Ratio
Weight
M-H,Random,95% CI
Risk Ratio
M-H,Random,95% CI
Total events: 13 (Calcium Carbonicum), 1 (Placebo)
0.02
0.1
Favours placebo
1
10
50
Favours calcium carb
APPENDICES
Appendix 1. Cochrane search strategy
#1(molluscum contagiosum):ti,ab,kw
#2(mollusca):ti,ab,kw
#3MeSH descriptor Molluscum Contagiosum explode all trees
#4(#1 OR #2 OR #3)
#5SR-SKIN
#6(#4 AND NOT #5)
Appendix 2. MEDLINE (OVID) search strategy
1. randomized controlled trial.pt.
2. controlled clinical trial.pt.
3. randomized.ab.
4. placebo.ab.
5. clinical trials as topic.sh.
6. randomly.ab.
7. trial.ti.
8. 1 or 2 or 3 or 4 or 5 or 6 or 7
9. (animals not (human and animals)).sh.
10. 8 not 9
11. molluscum contagiosum.mp. or exp Molluscum Contagiosum/
12. mollusca contagiosum.mp.
13. 11 or 12
14. 13 and 10
45
Appendix 3. EMBASE (OVID)search strategy
1. random$.mp.
2. factorial$.mp.
3. crossover$.mp.
4. placebo$.mp. or PLACEBO/
5. (doubl$ adj blind$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer,
drug manufacturer name]
6. (singl$ adj blind$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer,
drug manufacturer name]
7. assign$.mp.
8. volunteer$.mp. or VOLUNTEER/
9. Crossover Procedure/
10. Double Blind Procedure/
11. Randomized Controlled Trial/
12. Single Blind Procedure/
13. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12
14. molluscum contagiosum.mp. or exp Molluscum Contagiosum/
15. mollusca contagiosum.mp.
16. 14 or 15
17. 13 and 16
Appendix 4. LILACS search strategy
((Pt RANDOMIZED CONTROLLED TRIAL OR Pt CONTROLLED CLINICAL TRIAL OR Mh RANDOMIZED CONTROLLED TRIALS OR Mh RANDOM ALLOCATION OR Mh DOUBLE-BLIND METHOD OR Mh SINGLE-BLIND
METHOD OR Pt MULTICENTER STUDY) OR ((tw ensaio or tw ensayo or tw trial) and (tw azar or tw acaso or tw placebo or
tw control$ or tw aleat$ or tw random$ or (tw duplo and tw cego) or (tw doble and tw ciego) or (tw double and tw blind)) and tw
clinic$)) AND NOT ((CT ANIMALS OR MH ANIMALS OR CT RABBITS OR CT MICE OR MH RATS OR MH PRIMATES
OR MH DOGS OR MH RABBITS OR MH SWINE) AND NOT (CT HUMAN AND CT ANIMALS)) [Palavras] and molluscum
contagiosum [Palavras] or molusco contagioso [Palavras]
WHAT’S NEW
Last assessed as up-to-date: 7 June 2009.
7 December 2009
Amended
Unpublished data (Short 2002) has now been published as Short 2006.
HISTORY
Protocol first published: Issue 2, 2004
Review first published: Issue 2, 2006
46
22 July 2009
New search has been performed
New search, 6 new trials added. ’Risk of bias’ table
added, discussion rearranged, various minor adaptations.
21 June 2008
Amended
Converted to new review format.
6 December 2005
New citation required and conclusions have changed
Substantive amendment
CONTRIBUTIONS OF AUTHORS
Link with editorial base and co-ordination of contributions from co-authors: JCvdW
Protocol: JCvdW, SG, with contributions from all
Searches: SG, JM, JCvdW. Update 2009: RvdS, JCvdW
Screening abstracts: SG, JM, JCvdW. Update 2009: RvdS, JCvdW
Obtaining copies of trials: SG, JCvdW. Update 2009: RvdS, JCvdW
Assessing full papers for inclusion: SK, LvSS, MYB, JCvdW. Update 2009: RvdS, JCvdW
Extracting data from trials: CB, MYB, SK, JCvdW. Update 2009: RvdS, JCvdW
Assessing methodological quality: SG, SK, MB, JCvdW. Update 2009: RvdS, JCvdW
Data entry: JM, JCvdW. Update 2009: RvdS, JCvdW
Text of review: JM, JCvdW, with contributions from all. Update 2009: RvdS, JCvdW, with contributions from co-authors.
Consumer feedback on synopsis: MJAT
DECLARATIONS OF INTEREST
Anthony Ormerod who acted as a clinical content expert is also the author of one of the included trials. There has been no conflict of
interest.
SOURCES OF SUPPORT
Internal sources
• Department of General Practice, Erasmus MC, Rotterdam, Netherlands.
47
External sources
• No sources of support supplied
DIFFERENCES BETWEEN PROTOCOL AND REVIEW
The title of the published protocol was inadvertently left as ’Interventions for molluscum contagiosum in children’ although the decision
had already been made not to restrict the review to children.
Under ’Secondary outcome measures’ (b) and (g) were not initially specified in the protocol, but were added afterwards since improvement at the end of the study was frequently the most commonly reported outcome measure, and disease-related quality of life was
considered to be a relevant additional measure.
Under ’Selection of studies’ if an RCT included a variety of skin diseases, including molluscum contagiosum, the number of molluscum
participants needed to be at least five in the active treatment and placebo groups. This criterion was added after the protocol was
approved when a study was found which included 10 molluscum participants with a 9:1 distribution over the two treatment groups (
Caballero 1996). The criterion also applied to Manchanda 1997a.
Under ’Assessment of Risk of bias’ Items (d), (e), and (f ) were different from the original protocol or absent. They were added for the
2009 update, as recommended in the Handbook (Higgins 2008).
INDEX TERMS
Medical Subject Headings (MeSH)
Anti-Infective Agents, Local [therapeutic use]; Cimetidine [therapeutic use]; Hydroxides [therapeutic use]; Molluscum Contagiosum
[drug therapy; ∗ therapy]; Phytotherapy [methods]; Potassium Compounds [therapeutic use]; Povidone-Iodine [therapeutic use]; Randomized Controlled Trials as Topic; Remission, Spontaneous; Salicylic Acid [therapeutic use]; Sodium Nitrite [therapeutic use]
MeSH check words
Humans
48

Interventions for cutaneous molluscum contagiosum (Review) S

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