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Keywords:

  • Humans;
  • 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]

Abstract

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. References

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.

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

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. References

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 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 (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 T-cell 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.

Methods

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. References

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
Short-term clinical cure

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".

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).

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 long-term), 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

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. References

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.

Table 1. Treatment modalities and examples of references
Treatment classTreatment modalityIncluded studiesOther studies
Surgical treatmentsCryotherapy Caballero 1996; Barton 2002; Salmanpour 2006
 CurettageHanna 2006de Waard 1990
 Curettage with punch Quan 2000
 Electric cauterisation He 2001
 Physical expression (squeezing) Weller 1999
 Pricking Wishart 1903
 Pulsed dye laser Hammes 2001
Topical treatmentsAcidified nitriteOrmerod 1999Gräfe 2000
 Australian lemon myrtle oilBurke 2004 
 Benzoyl peroxideSaryazdi 2004 
 Bromogeramine He 2001
 CantharidinHanna 2006Funt 1961; Funt 1979; Silverberg 2000; Ross 2004
 Cidofovir Davies 1999; Zabawski 1999; Toro 2000
 Diphencyprone Kyu 1993; Kang 2005
 Griseofulvin Salmanpour 2006
 ImiquimodTheos 2004; Hanna 2006Syed 1998; Liota 2000; Barba 2001; Skinner 2002; Bayerl 2003; Hengge 2003
 Milkweed Behl 1970
 Povidone iodine + salicylic acidOhkuma 1990 
 PhenolLeslie 2005Weller 1999
 Podophyllotoxin (HIV patients) Syed 1994; Teilla-Hamel 1996; Markos 2001
 Potassium hydroxideBazza; Short 2006Romiti 1999; Romiti 2000
 Retinoic acid Hund 1975
 Salicylic acidOhkuma 1990; Leslie 2005; Hanna 2006 
 Salicylic acid combined with sodium nitriteOrmerod 1999 
 Silver nitrate Niizeki 1999
 TretinoinSaryazdi 2004 
 Yellow oxide of mercury Davis 1896
Systemic treatmentsCimetidineAntony 2001Dohil 1996; Cunningham 1998; Sharma 1998; Yasher 1999
 Calcarea carbonica (homeopathy)Manchanda 1997bManchanda 1997a
 Griseofulvin Singh 1977
Combinations of abovePotassium iodide followed by X-rays 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 cross-over 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 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. Thirty-eight 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.

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 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

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. References

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 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.

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Figure 1. Risk of bias table: review authors' judgements about each methodological quality item for each included study.

Download figure to PowerPoint

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 clear-cut 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 2006Bath-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

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. References

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, disease-related 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

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. References

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 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.

Characteristics of studies

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. References

Characteristics of included studies [ordered by study ID]

Antony 2001
MethodsDouble-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
Participants38 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
Interventions35 mg/kg/day cimetidine, given once daily as oral suspension versus a matching placebo
OutcomesComplete clearance after 4 months treatment. Reduction of lesions. Adverse events: not mentioned
Notes50% dropout rate. Published abstract only
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation?UnclearQuote: "Randomized". No details in abstract
Allocation concealment?UnclearMethod of concealment is not described in the abstract
Blinding? All outcomesYesQuote: "Double-blind placebo-controlled"; "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)UnclearNot reported in the abstract
Incomplete outcome data addressed? Medium and long-term outcomes (3 and 6 months)No4 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?UnclearUnclear
Free of other bias?UnclearQuote: "The mean age and sex of the patients and incidence of atopic disease in each treatment group was similar." No compliance data
Bazza
MethodsRandomised controlled trial. Body sides were randomised left-right. UK, Dept of Dermatology
Participants30 children (2 to 12 years of age, M/F 18/12) were recruited
InterventionsSterile normal 0.9% saline versus 5% potassium hydroxide
OutcomesComplete clearance of lesions; side-effects
NotesUnpublished, year of study unclear. Unpublished paper obtained in 2007
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation?UnclearQuote: "Where treatment with 0.9% NS and 5% KOH solution was randomized to right or left side of body". Insufficient information
Allocation concealment?UnclearQuote: "Where treatment with 0.9% NS and 5% KOH solution was randomized to right or left side of body". Insufficient information
Blinding? All outcomesYesQuote: "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)"
Incomplete outcome data addressed? Short-term outcomes (1 month)UnclearUnknown when patients dropped out, no short-term outcomes provided
Incomplete outcome data addressed? Medium and long-term outcomes (3 and 6 months)No12 weeks: 10/30 did not complete study, 2 withdrew due to severe stinging from KOH, and 8 children were lost to follow-up. > 30% drop-outs
Free of selective reporting?UnclearUnclear
Free of other bias?UnclearNo baseline comparison. No compliance data
Burke 2004
MethodsRandomised controlled trial, USA, outpatient clinic
Participants31 children, mean age 4.6 years. Sex not reported
Interventions10% lemon myrtle oil or vehicle (olive oil)
OutcomesComplete clearance or > 90% reduction in number of lesions
Notes-
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation?YesQuote: "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"
Allocation concealment?YesQuote: "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 outcomesYesQuote: "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
Incomplete outcome data addressed? Short-term outcomes (1 month)Yes21 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
Incomplete outcome data addressed? Medium and long-term outcomes (3 and 6 months)UnclearThe study did not address medium and long-term outcomes
Free of selective reporting?UnclearUnclear
Free of other bias?UnclearThe mean number of lesions at enrolment did not differ between treatment groups. No sex or age comparison between groups. No compliance data
Hanna 2006
MethodsRandomised controlled trial, Canada, Montreal, Dermatology clinic
Participants124 children, 1 to 16 years of age M/F 57/67
InterventionsFour arms: curettage; topical cantharidin 0.7%; topical salicylic acid 16.7% + lactic acid 16.7%; topical imiquimod cream 5%
OutcomesNumber of visits required. Intervals between study visits not reported, so outcome data not suitable for inclusion
NotesTotal number of patients unclear. Percentage of group 3 in table 1 does not correspond to number mentioned in text
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation?YesQuote: "The randomization list was generated by specialized computer software (PC-PLAN, Dalal, 1996)"
Allocation concealment?UnclearQuote: "The randomization list was generated by specialized computer software (PC-PLAN, Dalal, 1996)." Insufficient information
Blinding? All outcomesNoQuote: "This is not a double-blind study." Physical versus topical treatment
Incomplete outcome data addressed? Short-term outcomes (1 month)UnclearNot reported
Incomplete outcome data addressed? Medium and long-term outcomes (3 and 6 months)UnclearNot reported
Free of selective reporting?UnclearUnclear
Free of other bias?UnclearNo baseline comparison. No compliance data
Leslie 2005
MethodsRandomised controlled trial. UK, outpatient departments of teaching hospital and district general hospital
Participants114 children, 1 to 15 years of age, sex not reported
InterventionsTopical salicylic acid 12%, or phenol 10% with 70% alcohol, or 70% alcohol
OutcomesComplete clearance of lesions
Notes-
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation?YesQuote: "The participants were randomized according to a random number table"
Allocation concealment?NoQuote: "The investigators were not blinded to randomization"
Blinding? All outcomesNoQuote: "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"
Incomplete outcome data addressed? Short-term outcomes (1 month)UnclearUp 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
Incomplete outcome data addressed? Medium and long-term outcomes (3 and 6 months)NoUp 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 
Free of selective reporting?UnclearUnclear
Free of other bias?UnclearQuote: "The baseline characteristics of the three groups were similar." See also Table I, Baseline characteristics. No compliance data
Manchanda 1997b
MethodsDouble-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
Participants14 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)
InterventionsDifferent potencies of a homeopathic drug called calcarea carbonica daily for 15 days (n = 14) versus sugar globules (placebo). Unclear which patients received what potency
OutcomesImprovement (not clear after what period)
NotesPaper 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
ItemAuthors' judgementDescription
Adequate sequence generation?UnclearQuote: "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)
Allocation concealment?UnclearQuote: "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 outcomesYesQuote: "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
Incomplete outcome data addressed? Short-term outcomes (1 month)Yes15 days: 20/124 dropouts, unclear what skin disease and group assignment
Incomplete outcome data addressed? Medium and long-term outcomes (3 and 6 months)NoOnly 15 days
Free of selective reporting?UnclearUnclear
Free of other bias?UnclearNo baseline comparison. No compliance data
Ohkuma 1990
MethodsRandomised 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
Participants35 patients with molluscum contagiosum, aged between 2 and 9 years (M/F 21/14)
Interventions3 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)
OutcomesTime to cure Adverse events Study duration unknown
Notes-
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation?UnclearRandomised (personal communication, not in paper). Insufficient information about the sequence generation
Allocation concealment?UnclearInsufficient information about the sequence generation
Blinding? All outcomesNoProbably not, iodine versus salicylic plaster: hard to mask
Incomplete outcome data addressed? Short-term outcomes (1 month)UnclearNo loss reported, all patients in outcome table. Follow-up period unclear. Duration of treatment varied from 7 to 64 days
Incomplete outcome data addressed? Medium and long-term outcomes (3 and 6 months)UnclearNo loss reported, all patients in outcome table. Follow-up period unclear. Duration of treatment varied from 7 to 64 days
Free of selective reporting?UnclearUnclear
Free of other bias?UnclearQuote: "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
MethodsGroup 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
Participants30 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
Interventions5% sodium nitrite co-applied daily with 5% salicylic acid under occlusion versus identical cream with 5% salicylic acid omitting sodium nitrite
OutcomesTime to complete resolution Adverse events Study duration 3 months
Notes-
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation?UnclearQuote: "Group sequential design in which subjects were randomized to receive either". Insufficient information about the sequence generation
Allocation concealment?UnclearMethod of concealment not described
Blinding? All outcomesNoQuote: "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
Incomplete outcome data addressed? Short-term outcomes (1 month)UnclearOnly long-term data
Incomplete outcome data addressed? Medium and long-term outcomes (3 and 6 months)No21/30 dropouts after 3 months
Free of selective reporting?UnclearUnclear
Free of other bias?UnclearNo compliance data. Duration and number of lesions were very similar (communication with author)
Saryazdi 2004
MethodsRandomised trial, Iran, hospital dermatology clinic Outcomes given for 23 patients of 30 randomised, original distribution unknown, assumed 15:15
Participants30 children, age and sex unknown
InterventionsTopical benzoyl peroxide 10% cream versus tretinoin 0.05% cream, 2 times daily (TD) for 4 weeks
OutcomesCount of lesions, lesion free after 6 weeks Side-effects limited to mild dermatitis in both groups
NotesInformation based on abstract, proportions cured used for estimating absolute numbers. Abstract published in 2004 - unclear when study was carried out
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation?UnclearNot reported
Allocation concealment?UnclearNot reported
Blinding? All outcomesUnclear"Investigator masked"
Incomplete outcome data addressed? Short-term outcomes (1 month)UnclearNot reported
Incomplete outcome data addressed? Medium and long-term outcomes (3 and 6 months)UnclearNot reported
Free of selective reporting?UnclearUnclear
Free of other bias?UnclearNo baseline characteristics nor compliance data
Short 2006
MethodsDouble-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.
Participants20 children from a paediatric dermatology clinic, age range 2 to 12 years, M/F 6/14. Exclusion criteria were known immunodeficiency and facial lesions
InterventionsApplication 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)
OutcomesTime to resolution Adverse events Study duration 3 months
NotesNumber 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).
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation?UnclearQuote: "The children were randomly allocated by the dispensing pharmacist to receive one of two treatments". Insufficient information.
Allocation concealment?UnclearQuote: "The children were randomly allocated by the dispensing pharmacist to receive one of two treatments." Central allocation: Pharmacy-controlled
Blinding? All outcomesYesQuote: "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
Incomplete outcome data addressed? Short-term outcomes (1 month)Yes2 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
Incomplete outcome data addressed? Medium and long-term outcomes (3 and 6 months)Yes90 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
Free of selective reporting?UnclearUnclear
Free of other bias?UnclearNo baseline imbalance for sex, lesion site, and numbers. No compliance data
Theos 2004
  1. KOH = Potassium Hydroxide

  2. NS = Normal Saline

MethodsRandomised controlled trial. USA, Alabama, Illinois, New York
Participants23 children, 1 to 9 years of age, M/F 12/11
InterventionsImiquimod cream 5% or vehicle
OutcomesComplete or partial clearance (> 30% decrease from baseline lesion count)
Notes-
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation?UnclearQuote: "Eligible patients were randomized to either imiquimod or vehicle". Insufficient information
Allocation concealment?UnclearQuote: "Eligible patients were randomized to either imiquimod or vehicle". Insufficient information
Blinding? All outcomesYesQuote: "In a Double Blind, Randomized Pilot Trial"; "imiquimod vs vehicle". Only patients and physicians involved
Incomplete outcome data addressed? Short-term outcomes (1 month)Yes2 weeks: 2/23 not completed the study (discontinued treatment)
Incomplete outcome data addressed? Medium and long-term outcomes (3 and 6 months)Yes2 weeks: 2/23 not completed the study (discontinued treatment)
Free of selective reporting?UnclearUnclear
Free of other bias?UnclearBaseline imbalance for mean lesion count, imiquimod: 27.0 versus vehicle: 19.4 (not statistically significant). No compliance data

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Barton 2002HIV-infected patients (n = 40)
Caballero 1996RCT comparing 2 types of cryotherapy for cutaneous skin lesions: 124 patients, among which 10 molluscum patients, distributed 9:1 over 2 arms
Chatproedrai 2007Not randomised (personal communication)
de Waard 1990Study on analgesic effect of lidocaine/prilocaine (EMLA) cream before physical therapy. Not a focus of this review (n = 83)
He 2001Large parallel controlled study (n = 1656), with 4 arms, no randomisation (personal communication with Dr He through Taixiang Wu)
Juhlin 1980Study on analgesic effect of lidocaine/prilocaine (EMLA) cream before physical therapy. Not a focus of this review (n = 24)
Manchanda 1997aCross-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 1988Study on analgesic effect of lidocaine/prilocaine (EMLA) cream before physical therapy. Not a focus of this review (n = 55)
Salmanpour 2006Not randomised but alternate assignment (personal communication, Alireza Firooz)
Syed 1994RCT, n = 150, mainly genital lesions, which is not a focus of this review
Syed 1998RCT, n = 100, mainly genital lesions, which is not a focus of this review
Weller 1999Controlled trial (n = 16), comparing phenol ablation and physical expression. Lesions were unit of treatment and analysis. No randomisation
Yabut-Catalasan 2003Controlled trial, N=34, aged 2 to 12 years. 10% potassium hydroxide versus placebo. Not randomised, but alternate assignment

Characteristics of ongoing studies [ordered by study ID]

NCT00667225
Trial name or titleEfficacy of cantharidin in molluscum contagiosum: a randomised, blinded, placebo-controlled prospective study
MethodsRandomized, double-blind (subject, caregiver, investigator, outcomes assessor)
ParticipantsMolluscum patients
InterventionsTopical cantharidin 0.7% Vehicle
OutcomesComplete and partial clearance after 8 weeks or 5 visits
Starting dateJanuary 2008
Contact informationjacquelyn.coloe@osumc.edu
Notes-

Data and analyses

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. References
Table Comparison 1.. Topical: 10% Australian lemon myrtle oil vs. vehicle (olive oil)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Complete clearance or > 90% reduction after 3 weeks131Risk Ratio (M-H, Fixed, 95% CI)17.88 [1.13, 282.72]
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Figure 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.

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Table Comparison 2.. Topical: 5% imiquimod vs. vehicle
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Complete clearance after 4 weeks123Risk Ratio (M-H, Fixed, 95% CI)4.62 [0.25, 86.72]
2 Partial clearance after 4 weeks123Risk Ratio (M-H, Fixed, 95% CI)13.85 [0.88, 217.26]
3 Complete clearance after 12 weeks123Risk Ratio (M-H, Fixed, 95% CI)3.67 [0.48, 28.00]
4 Partial clearance after 12 weeks123Risk Ratio (M-H, Fixed, 95% CI)3.67 [0.98, 13.67]
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Figure Analysis 2.1. Comparison 2 Topical: 5% imiquimod vs. vehicle, Outcome 1 Complete clearance after 4 weeks.

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Figure Analysis 2.2. Comparison 2 Topical: 5% imiquimod vs. vehicle, Outcome 2 Partial clearance after 4 weeks.

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Figure Analysis 2.3. Comparison 2 Topical: 5% imiquimod vs. vehicle, Outcome 3 Complete clearance after 12 weeks.

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Figure Analysis 2.4. Comparison 2 Topical: 5% imiquimod vs. vehicle, Outcome 4 Partial clearance after 12 weeks.

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Table Comparison 3.. Topical: 10% benzoyl peroxide cream vs. 0.05% tretinoin cream (ITT)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Free of lesions after 6 weeks130Risk Ratio (M-H, Fixed, 95% CI)2.2 [1.01, 4.79]
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Figure Analysis 3.1. Comparison 3 Topical: 10% benzoyl peroxide cream vs. 0.05% tretinoin cream (ITT), Outcome 1 Free of lesions after 6 weeks.

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Table Comparison 4.. Topical: 10% KOH vs. saline
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Clinical cure at medium-term follow-up (3 months)260Risk Ratio (M-H, Random, 95% CI)1.68 [0.36, 7.75]
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Figure Analysis 4.1. Comparison 4 Topical: 10% KOH vs. saline, Outcome 1 Clinical cure at medium-term follow-up (3 months).

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Table Comparison 5.. Topical: 10% povidone iodine and 50% salicylic plaster vs. 10% povidone iodine alone
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Clinical cure at end of study (duration unknown)125Risk Ratio (M-H, Random, 95% CI)1.67 [0.85, 3.30]
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Figure Analysis 6.1. 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).

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Table Comparison 6.. Topical: 10% povidone iodine and 50% salicylic acid plaster vs. 50% salicylic plaster alone
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Clinical cure at end of study (duration unknown)130Risk Ratio (M-H, Random, 95% CI)1.43 [0.95, 2.16]
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Figure 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).

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Table Comparison 7.. Topical: 10% povidone iodine vs. 50% salicylic acid plaster
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Clinical cure at end of study (duration unknown)115Risk Ratio (M-H, Random, 95% CI)0.86 [0.38, 1.95]
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Figure Analysis 7.1. Comparison 7 Topical: 10% povidone iodine vs. 50% salicylic acid plaster, Outcome 1 Clinical cure at end of study (duration unknown).

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Table Comparison 8.. Topical: 5% sodium nitrite in 5% salicylic acid vs. 5% salicylic acid alone
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Clinical cure at medium-term follow-up (3 months)130Risk Ratio (M-H, Random, 95% CI)3.5 [1.23, 9.92]
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Figure 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).

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Table Comparison 9.. Topical: 10% phenol/70% alcohol vs. 70% alcohol (ITT)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Complete clearance at end of study (max 6 months)177Risk Ratio (M-H, Fixed, 95% CI)0.93 [0.56, 1.56]
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Figure 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).

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Table Comparison 10.. Topical: 12% salicylic acid vs. 70% alcohol (ITT)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Complete clearance at end of study (6 months max)173Risk Ratio (M-H, Fixed, 95% CI)1.28 [0.81, 2.02]
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Figure Analysis 10.1. Comparison 10 Topical: 12% salicylic acid vs. 70% alcohol (ITT), Outcome 1 Complete clearance at end of study (6 months max).

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Table Comparison 11.. Topical: 12% salicylic acid vs. 10% phenol/70% alcohol (ITT)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Complete clearance at end of study (max 6 months)178Risk Ratio (M-H, Fixed, 95% CI)1.37 [0.86, 2.17]
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Figure 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).

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Table Comparison 12.. Systemic: cimetidine vs. placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Clinical cure at medium-term follow-up (4 months)119Risk Ratio (M-H, Random, 95% CI)1.1 [0.43, 2.84]
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Figure Analysis 12.1. Comparison 12 Systemic: cimetidine vs. placebo, Outcome 1 Clinical cure at medium-term follow-up (4 months).

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Table Comparison 13.. Systemic: calcarea carbonica vs. placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Improvement at end of study (duration unknown)120Risk Ratio (M-H, Random, 95% CI)5.57 [0.93, 33.54]
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Figure Analysis 13.1. Comparison 13 Systemic: calcarea carbonica vs. placebo, Outcome 1 Improvement at end of study (duration unknown).

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Appendices

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. References

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

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]

History

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. References

Protocol first published: Issue 2, 2004

Review first published: Issue 2, 2006

DateEventDescription
22 July 2009New search has been performedNew search, 6 new trials added. 'Risk of bias' table added, discussion rearranged, various minor adaptations.
21 June 2008AmendedConverted to new review format.
6 December 2005New citation required and conclusions have changedSubstantive amendment

Contributions of authors

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. References

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

Differences between protocol and review

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. References

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).

References

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. References
  • References to studies included in this review
  • Antony 2001 {published data only}
  • * Antony F, Cliff S, Ahmad A, Holden C. Double-blind placebo-controlled 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;58:2457.
  • 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):5749.
  • 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):33640.
  • 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;19:259.
  • Ohkuma 1990 {published data only}
  • * Ohkuma M. Molluscum contagiosum treated with iodine solution and salicylic acid plaster. International Journal of Dermatology 1990;29(6):4435.
  • 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):10513.
  • 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;23:27981.
  • 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).
  • 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;74:1348,141-2.
  • References to studies excluded from this review
  • Barton 2002 {published data only}
  • Barton SE, Chard S. Facial molluscum: treatment with cryotherapy and podophyllotoxin. International Journal of STD & AIDS 2002;13(4):2778.
  • Caballero 1996 {published data only}
  • Caballero Martinez F, Plaza Nohales C, Perez Canal C, Lucena Martin MJ. Cutaneous cryosurgery in family medicine: dimethyl ether-propane spray versus liquid nitrogen. Atencion Primaria 1996;18(5):2116.
  • Chatproedrai 2007 {published data only}
  • Chatproedrai S, Kamol S, Wananukul S, Theamboonlers A, Poovorawan Y. Efficacy of pulsed dye laser (585 nm) in the treatment of molluscum contagiosum subtype 1. Southeast Asian Journal of Tropical Medicine & Public Health 2007;38(5):84954.
  • de Waard 1990 {published data only}
  • de Waard-van der Spek FB, Oranje AP, Lillieborg S, Hop WC, Stolz E. Treatment of molluscum contagiosum using a lidocaine/prilocaine cream (EMLA) for analgesia. Journal of the American Academy of Dermatology 1990;Oct(4 Pt 1):6858.
  • He 2001 {published data only}
  • He H, Lu JY, Fang J, et al.Observation on effect of four kinds of therapy for molluscum contagiosum (Chinese). Chinese Journal of Dermatovenereology 2001;15(5):3089.
  • Juhlin 1980 {published data only}
  • Juhlin L, Evers H, Broberg F. A lidocaine-prilocaine cream for superficial skin surgery and painful lesions. Acta Dermato-Venereologica (Stockholm) 1980;60(6):5446.
  • Manchanda 1997a {published data only}
  • Manchanda RK, Mehan N, Bahl R, Atey R. Double blind placebo controlled trials of homeopathic medicines in warts and molluscum contagiosum. Central Council for Research in Homeopathy Quarterly Bulletin 1997; Vol. 19 (3&4):2530.
  • Rosendahl 1988 {published data only}
  • Rosendahl I, Edmar B. Curettage of molluscum contagiosum in children: analgesia by topical application of lidocaine/prilocaine cream (EMLA). Acta Dermato-Venereologica (Stockholm) 1988;68:14953.
  • Salmanpour 2006 {published data only}
  • Salmanpour R. Treatment of molluscum contagiosum with griseofulvin or cryotherapy. Iranian Journal of Dermatology 2006;9(1):5.
  • Syed 1994 {published data only}
  • Syed TA, Lundin S, Ahmad M. Topical 0.3% and 0.5% podophyllotoxin cream for self-treatment of molluscum contagiosum in males. A placebo-controlled, double-blind study. Dermatology 1994;189(1):658.
  • Syed 1998 {published data only}
  • Syed TA, Goswami J, Ahmadpour OA, Ahmad SA. Treatment of molluscum contagiosum in males with an analog of imiquimod 1% in cream: a placebo-controlled, double-blind study. Journal of Dermatology 1998;25(5):30913.
  • Weller 1999 {published data only}
  • Weller R, O'Callaghan CJ, MacSween RM, White MI. Scarring in molluscum contagiosum: comparison of physical expression and phenol ablation. BMJ 1999;319(7224):1540.
  • Yabut-Catalasan 2003 {published data only}
  • Yabut-Catalasan RO, Paliza AC. 10% Potassium Hydroxide as treatment for molluscum contagiosum: a double-blind, placebo-controlled study. Journal of the Philippine Dermatological Society 2003;12(1):2835.
  • References to ongoing studies
  • NCT00667225 {published data only}
  • NCT00667225. Efficacy of cantharidin in molluscum contagiosum. ClinicalTrials.Gov/ct2/show/NCT00667225 (accessed 18 February 2009).
  • Additional references
  • Back Review Group 2008
  • Cochrane Back Review Group. Sources of risk of bias. http://www.cochrane.iwh.on.ca/pdfs/RoBassessform_June2008.rtf (accessed 3 February 2009).
  • Barba 2001
  • Barba AR, Kapoor S, Berman B. An open label safety study of topical imiquimod 5% cream in the treatment of molluscum contagiosum in children. Dermatology online 2001;7(1):20.
  • Bath-Hextall 2007
  • Bath-Hextall FJ, Perkins W, Bong J, Williams HC. Interventions for basal cell carcinoma of the skin. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD003412.
  • Bayerl 2003
  • Bayerl C, Feller G, Goerdt S. Experience in treating molluscum contagiosum in children with imiquimod 5% cream. British Journal of Dermatology 2003;149 Suppl 66:259.
  • Beaulieu 2000
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