Plain language summary
Treatments for molluscum contagiosum, a common viral skin infection in children
We reviewed the evidence for the effect of any treatment on the common viral skin infection molluscum contagiosum. We excluded people with a repressed immune system or sexually transmitted molluscum contagiosum.
Molluscum contagiosum in healthy people is a self limiting, relatively harmless viral skin infection. It mainly affects children and adolescents and is rare in adults. It occurs worldwide, but seems much more frequent in geographic areas with warm climates. Molluscum contagiosum usually presents as single or multiple pimples filled with an oily substance. People may seek treatment for social and cosmetic reasons and because of concerns about spreading the disease to others. Treatment is intended to speed up the healing process.
We searched the literature to July 2016. We included 22 trials (total of 1650 participants). Twenty of the studies evaluated topical treatment, and two studies evaluated treatment taken by mouth (oral). Comparisons included physical therapies, as well as topical and oral treatments. Most studies were set in hospital outpatient or emergency departments, and were performed in North America, the UK, Asia, or South America. Participants were of both sexes and were mainly children or young adults. Follow-up duration varied from 3 to 28 weeks after randomisation. Only five studies had longer than 3 months' follow-up.
Five studies reported commercial funding, three studies obtained medication for free from pharmaceutical companies, 12 studies did not mention the source of funding, one study reported charity funding, and one study reported they had had no financial support.
We found that many common treatments for molluscum, such as physical destruction, have not been adequately evaluated. Some of the included treatments are not part of standard practice.
We found moderate-quality evidence that topical 5% imiquimod is probably no more effective than vehicle (i.e. the same cream but without imiquimod) in achieving short-, medium-, and long-term clinical cure. High-quality (and thus more certain) evidence showed that topical 5% imiquimod is no better than placebo at improving molluscum up to three months after the start of treatment.
High-quality evidence showed that 5% imiquimod differed little or not at all in the number of side effects compared to vehicle. However, moderate-quality evidence suggests that there are probably more application site reactions when using topical 5% imiquimod compared with vehicle.
Low-quality evidence, based on one or two mostly small studies, revealed the following results for the outcome short-term clinical cure: 5% imiquimod less effective than cryospray or 10% potassium hydroxide; 10% Australian lemon myrtle oil more effective than olive oil; 10% benzoyl peroxide cream more effective than 0.05% tretinoin; 5% sodium nitrite co-applied with 5% salicylic acid more effective than 5% salicylic acid alone; and iodine plus tea tree oil more effective than tea tree oil or iodine alone. We found more uncertain (low-quality) evidence to suggest that 10% potassium hydroxide is more effective than saline; homeopathic calcarea carbonica is more effective than placebo; 2.5% solution of potassium hydroxide is less effective than 5% solution of potassium hydroxide; and 10% povidone iodine solution and 50% salicylic acid plaster are more effective than salicylic acid plaster alone.
Except for the severe application site reactions of imiquimod, none of these treatments led to serious adverse effects (low-quality evidence). Pain during treatment application, redness, and itching were among the most reported adverse effects.
We found no differences between the treatments assessed in the other comparisons.
We found no randomised trials for several commonly used treatments, such as expressing lesions with an orange stick or topical hydrogen peroxide. Since most lesions resolve within months, unless better evidence for the superiority of active treatments emerges, molluscum contagiosum can be left to heal naturally.
Quality of the evidence
For topical imiquimod, the quality of the evidence for clinical cure, short-term improvement, and adverse effects was moderate to high. For all other comparisons, the quality of the evidence for short-term clinical cure and adverse effects was low. Common limitations of the included studies were that the numbers of participants were small, the investigators were not blinded, and participants who did not complete the study (numerous in some studies) were not included in the analyses.
Les traitements contre le molluscum contagiosum, une infection virale de la peau courante chez les enfants
Question de la revue
Nous avons examiné les preuves concernant les effets de n'importe quel traitement sur l'infection virale et courante de la peau appelée molluscum contagiosum. Nous avons exclu les personnes ayant un système immunitaire atténué ou un molluscum contagiosum sexuellement transmissible.
Le molluscum contagiosum chez les personnes en bonne santé est une infection virale de la peau relativement inoffensive et guérissant d'elle-même. Celle-ci touche principalement les enfants et les adolescents et est rare chez l'adulte. Elle survient dans le monde entier, mais semble beaucoup plus fréquente dans les zones géographiques au climat chaud. Le molluscum contagiosum se présente généralement sous la forme d'un ou de plusieurs boutons contenant des liquides huileux. Ces personnes peuvent avoir recours à un traitement pour des raisons sociales et esthétiques et parce qu'elles craignent de transmettre la maladie. Le traitement vise à accélérer le processus de guérison.
Caractéristiques de l'étude
Nous avons effectué des recherches dans la littérature jusqu'en juillet 2016. Nous avons inclus 22 études (ayant un total de 1650 participants). Vingt de ces études évaluaient le traitement appliqué sur la peau (topique), et deux études évaluaient le traitement pris par la bouche (par voie orale). Les comparaisons comprenaient des thérapies mécaniques, ainsi que des traitements topiques et oraux. La plupart des études avaient été réalisées en milieu hospitalier ambulatoire ou dans des services d'urgence, et ont été réalisées en Amérique du Nord, au Royaume-Uni, en Asie, ou en Amérique du Sud. Les participants étaient des deux sexes et étaient principalement des enfants ou de jeunes adultes. La durée de suivi variait de 3 à 28 semaines après la randomisation. Seules cinq études avaient des périodes de suivi supérieures à 3 mois.
Cinq études ont rapporté un financement commercial, trois études ont obtenu des médicaments gratuitement auprès de sociétés pharmaceutiques, 12 études ne mentionnaient pas leurs sources de financement, une étude rapportait un financement provenant d'une organisation caritative, et une étude rapportait qu'ils n'avaient reçu aucun soutien financier.
Nous avons trouvé que de nombreux traitements communs contre le molluscum, tels que la destruction physique, n'ont pas été correctement évalués. Certains des traitements inclus ne font pas partie des soins standard.
Nous avons trouvé des preuves de qualité modérée indiquant que l'imiquimod topique à 5 % n'est probablement pas plus efficace que son excipient (c'est-à-dire la même crème mais sans l'imiquimod) pour atteindre à court, moyen et long terme une guérison. Des preuves de haute qualité (et offrant ainsi une plus haute certitude) ont montré que l'imiquimod topique à 5 % n'est pas plus efficace que le placebo pour améliorer les molluscums jusqu'à trois mois après le début du traitement.
Des preuves de haute qualité ont montré que l'imiquimod à 5 % avait des effets similaires au niveau du nombre d'effets secondaires par rapport à l'excipient seul. Cependant, des preuves de qualité modérée suggèrent qu'il existe probablement davantage de réactions au point d'application de la crème lors de l'utilisation de l'imiquimod à 5 % par rapport à l'excipient seul.
Des preuves de faible qualité, sur la base d'une ou deux études, principalement de petite taille ont révélé les résultats suivants concernant le résultat à court terme de la guérison clinique : l'imiquimod à 5 % était moins efficace que le cryospray ou l'hydroxyde de potassium à 10 % ; l'huile de myrte citronnée d'Australie à 10 % état plus efficace que l'huile d'olive ; la crème à base de peroxyde de benzoyle à 10 % était plus efficace que la trétinoïne à 0,05 % ; le nitrite de sodium à 5 % associé à de l'acide salicylique à 5 % était plus efficace que l'acide salicylique à 5 % seul ; et l'iode associée à de l'huile provenant de l'arbre à thé était plus efficace que l'huile d'arbre à thé ou l'iode seuls. Nous avons trouvé des preuves plus incertaines (de faible qualité) suggérant que l'hydroxyde de potassium à 10 % est plus efficace qu'une solution saline ; que le calcarea carbonica homéopathique est plus efficace qu'un placebo ; qu'une solution d'hydroxyde de potassium à 2,5 % est moins efficace qu'une solution d'hydroxyde de potassium à 5 %; et qu'une solution de povidone iodée à 10 % associée à un plâtre d'acide salicylique à 50 % sont plus efficaces que le plâtre à l'acide salicylique seul.
En dehors de réactions sévères au site d'application de l'imiquimod, aucun de ces traitements n'a conduit à de graves effets indésirables (preuves de faible qualité). Les effets indésirables les plus fréquemment rapportés étaient des douleurs pendant l'application du traitement, des démangeaisons et des rougeurs.
Nous n'avons trouvé aucune différence entre les traitements évalués dans les autres comparaisons.
Nous n'avons trouvé aucun essai randomisé pour plusieurs traitements couramment utilisés, tels que percer les lésions avec un bâtonnet ou l'application de peroxyde d'hydrogène sur la peau. Etant donné que la plupart des lésions guérissent spontanément en quelques mois, et en l'absence de meilleures preuves indiquant une supériorité des traitements actifs d'urgence, il est possible de laisser le molluscum contagiosum guérir spontanément.
Qualité des preuves
Concernant l'imiquimod topique, la qualité des preuves concernant la guérison clinique, l'amélioration à court terme, et les effets indésirables était modérée à élevée. Pour toutes les autres comparaisons, la qualité des preuves à court terme pour la guérison clinique et les effets indésirables était faible. Les limitations habituelles des études étaient un nombre limité de participants, des investigateurs sachant ce que les participants recevaient, et les participants n'ayant pas terminé l'étude (nombreux dans certaines études) n'ont pas été inclus dans les analyses.
Notes de traduction
Traduction réalisée par Martin Vuillème et révisée par Cochrane France
Resumen en términos sencillos
Tratamientos para el molusco contagioso, una infección viral común de la piel en los niños
Pregunta de la revisión
Se examinó la evidencia del efecto de cualquier tratamiento sobre la infección viral común de la piel, molusco contagioso. Se excluyó a los pacientes con un sistema inmunológico reprimido o con molusco contagioso de transmisión sexual.
El molusco contagioso en los pacientes sanos es una infección viral de la piel relativamente inocua que se resuelve de forma espontánea. Afecta principalmente a niños y adolescentes y es poco frecuente en adultos. Ocurre en todo el mundo, aunque parece mucho más frecuente en las zonas geográficas con climas cálidos. El molusco contagioso se presenta por lo general como granos únicos o múltiples llenos de una sustancia aceitosa. Los pacientes pueden buscar tratamiento por razones sociales y estéticas y debido a las inquietudes relacionadas con la transmisión de la enfermedad a otros. El tratamiento está orientado a acelerar el proceso curativo.
Características de los estudios
Se hicieron búsquedas en la literatura hasta julio 2016. Se incluyeron 22 ensayos (total de 1650 participantes). Veinte de los estudios evaluaron el tratamiento tópico, y dos estudios evaluaron el tratamiento administrado por vía oral. Las comparaciones incluyeron fisioterapias, así como tratamientos tópicos y orales. La mayoría de los estudios se realizaron en ámbitos hospitalarios ambulatorios o de urgencias y fueron llevados a cabo en Norteamérica, el Reino Unido, Asia, o América del Sur. Los participantes eran de ambos sexos y eran principalmente niños o adultos jóvenes. La duración del seguimiento varió de tres a 28 semanas después de la asignación al azar. Sólo cinco estudios tuvieron más de tres meses de seguimiento.
Cinco estudios informaron el financiamiento comercial, tres estudios obtuvieron medicación de forma gratuita por parte de compañías farmacéuticas, 12 estudios no mencionaron la fuente de financiamiento, un estudio informó financiamiento de organizaciones benéficas y un estudio informó que no había recibido apoyo económico.
Se encontró que muchos tratamientos comunes para el molusco, como la destrucción física, no se han evaluado de forma adecuada. Algunos de los tratamientos incluidos no son parte de la práctica estándar.
Se encontró evidencia de calidad moderada de que el imiquimod al 5% tópico probablemente no es más efectivo que el vehículo (es decir la misma crema pero sin imiquimod) para lograr la curación clínica a corto, a medio y a largo plazo. La evidencia de alta calidad (y por lo tanto más certera) indicó que el imiquimod al 5% tópico no es mejor que el placebo para mejorar el molusco hasta tres meses después del comienzo del tratamiento.
La evidencia de alta calidad indicó que el imiquimod al 5% difirió poco o nada en el número de efectos secundarios en comparación con el vehículo. Sin embargo, la evidencia de calidad moderada indica que probablemente hay más reacciones en el sitio de aplicación al utilizar imiquimod al 5% tópico en comparación con el vehículo.
La evidencia de baja calidad, basada en uno o dos estudios principalmente pequeños, reveló los siguientes hallazgos para el resultado de la curación clínica a corto plazo: imiquimod al 5% menos efectivo que el criospray o que el hidróxido de potasio al 10%; aceite de mirto limón australiano al 10% más efectivo que el aceite de oliva; crema de peróxido de benzoilo al 10% más efectiva que la tretinoina al 0,05%; nitrito de sodio al 5% coaplicado con ácido salicílico al 5% más efectivo que el ácido salicílico al 5% solo; e yodo más aceite del árbol de té más efectivo que el aceite del árbol de té o el yodo solo. Se encontró más evidencia incierta (de baja calidad) que indicaba que el hidróxido de potasio al 10% es más efectivo que la solución salina; la calcárea carbónica homeopática es más efectiva que el placebo; la solución de hidróxido de potasio al 2,5% es menos efectiva que la solución de hidróxido de potasio al 5%; y la solución de yodo de povidona al 10% y el emplasto de ácido salicílico al 50% son más efectivos que el emplasto de ácido salicílico solo.
Excepto por las reacciones graves en el sitio de aplicación del imiquimod, ninguno de estos tratamientos dio lugar a efectos adversos graves (evidencia de baja calidad). El dolor durante la aplicación del tratamiento, el enrojecimiento y la picazón estuvieron entre los efectos adversos más informados.
No se encontraron diferencias entre los tratamientos evaluados en las otras comparaciones.
No se encontró ningún ensayo aleatorio para varios tratamientos utilizados comúnmente, como la expresión de las lesiones con un palillo de naranjo o el peróxido de hidrógeno tópico. Debido a que la mayoría de las lesiones se resuelve en meses, a menos que surja evidencia de mejor calidad sobre la superioridad de los tratamientos activos, se puede dejar que el molusco contagioso sane naturalmente.
Calidad de la evidencia
Para el imiquimod tópico, la calidad de la evidencia para la curación clínica, la mejoría a corto plazo y los efectos adversos fue moderada a alta. Para todas las otras comparaciones, la calidad de la evidencia para la curación clínica a corto plazo y los efectos adversos fue baja. Las limitaciones comunes de los estudios incluidos fueron que los números de participantes fueron reducidos, no se realizó el cegamiento de los investigadores, y los participantes que no finalizaron el estudio (numerosos en algunos estudios) no se incluyeron en los análisis.
Notas de traducción
La traducción y edición de las revisiones Cochrane han sido realizadas bajo la responsabilidad del Centro Cochrane Iberoamericano, gracias a la suscripción efectuada por el Ministerio de Sanidad, Servicios Sociales e Igualdad del Gobierno español. Si detecta algún problema con la traducción, por favor, contacte con Infoglobal Suport, firstname.lastname@example.org.
Načini liječenja vodenih bradavica (Molluscum contagiosum), česte virusne infekcije kože kod djece.
U ovom Cochrane sustavnom pregledu literature analizirani su dokazi o učinkovitosti različitih načina liječenja česte kožne virusne infekcije Molluscum contagiosum. Isključene su imunokompromitirane osobe i osobe zaražene spolnim putem.
Kod zdravih osoba, Molluscum contagiosum je samoograničavajuća, relativno bezopasna kožna infekcija. Uglavnom pogađa djecu i adolescente, rijetko odrasle. Rasprostranjena je u čitavom svijetu, no češće se javlja u područjima tople klime. Molluscum contagiosum se javljaju kao jedna ili nekoliko papula ispunjenih uljastim sadržajem. Liječenje se propisuje iz društvenih i kozmetičkih razloga ili zbog sprječavanja širenja zaraze na druge. Terapije imaju cilj ubrzavanje procesa zacjeljivanja.
Obilježja uključenih istraživanja
Pretražena je literatura objavljena do srpnja 2016. Uključena su 22 ispitivanja (ukupno 1650 sudionika). U dvadeset studija je ispitivano lokalno liječenje, a u dvije studije terapija koja se uzima na usta (oralna terapija). Usporedbe su uključivale fizikalnu, lokalnu i oralnu terapiju. Najveći broj studija proveden je u dnevnim bolnicama i hitnim službama u Sjevernoj Americi, Ujedinjenom Kraljevstvu, Aziji i Južnoj Americi. Sudionici su bili oba spola, uglavnom djeca ili mlade odrasle osobe. Period praćenja varirao je od 3 do 28 tjedana nakon razvrstavanja ispitanika. Samo je u pet studija period praćenja bio duži od 3 mjeseca.
Pet studija sponzorirano je komercijalno, u tri studije lijekovi su donirani od strane farmaceutskih kompanija, 12 studija nije navelo izvor financiranja, jedna studija je sponzorirana iz dobrotvornih izvora, a u jednoj studiji je prijavljeno da nije bilo financijske podrške.
Nađeno je da mnogi uobičajeni tretmani za liječenje moluski, poput mehaničkog uklanjanja, nisu primjereno procijenjene. Neki od uključenih tretmana nisu dio standardne prakse.
Nađeni su dokazi umjerene kvalitete da lokalni 5% imikvimod vjerojatno nije učinkovitiji od nosača (npr. iste kreme bez imikvimoda) u postizanju kratkoročnih, srednjih i dugoročnih kliničkih ishoda. Dokazi visoke kvalitete pokazali su da 5% imikvimod nije bolji od placeba u liječenju moluska u periodu do tri mjeseca nakon početka liječenja.
Dokazi visoke kvalitete pokazali su da se 5% imikvimod ne razlikuje puno po broju nuspojava u odnosu na nosač. No, dokazi srednje kvalitete ukazuju da vjerojatno postoji više reakcija na mjestu primjene kada se koristi 5% imikvimod u usporedbi s nosačem.
Dokazi niske kvalitete, temeljeni na jednoj ili dvije manje studije, pokazali su sljedeće rezultate kratkoročnih kliničkih ishoda: 5% imikvimod je manje učinkovit od kriospreja ili 10% kalij hidroksida; 10% ulje australske limunske mirte je učinkovitije od maslinovog ulja; 10% krema benzoil peroksida je učinkovitija od 0.5% tretinoina; 5% natrij nitrit primijenjen zajedno s 5% salicilnom kiselinom je učinkovitiji u odnosu na samu 5% salicilnu kiselinu; jod s uljem čajevca je učinkovitiji u odnosu na čajevac ili jod posebno. Pronađeno je više dokaza niske kvalitete koji predlažu da je 10% kalij hidroksid učinkovitiji u odnosu na fiziološku otopinu; homeopatska calcarea carbonica je učinkovitija u odnosu na placebo; 2.5% otopina kalij hidroksida ja manje učinkovita od 5% otopine, 10% povidon jod uz 50% flastere salicilne kiseline je učinkovitiji od samih flastera 50% salicilne kiseline.
Osim ozbiljnih reakcija na mjestu primjene imikvimoda, niti jedan od ovih načina liječenja nije doveo do ozbiljnih nuspojava (dokazi niske kvalitete). Najčešće prijavljene nuspojave su bol tijekom liječenja, crvenilo i svrbež.
Nisu nađene razlike između načina liječenja uspoređivanih u drugim procjenama.
Nisu pronađene randomizirane studije za neke od najučestalijih načina liječenja, poput primjene lokalnog hidrogen peroksida. Budući da se većina lezija povuče unutar nekoliko mjeseci, ukoliko se ne pojave bolji dokazi o prednosti korištenja određenog načina liječenja, zarazne moluske se može ostaviti da same prođu.
Za lokalni imikvimod, kvaliteta dokaza za kliničko izlječenje, kratkoročno poboljšanje i nuspojave je umjerena do visoka. Za sve druge usporedbe, kvaliteta dokaza kratkoročnih kliničkih ishoda i nuspojava je niska. Uobičajena ograničenja uključenih studija su malen broj sudionika, jednostruko slijepo ispitivanje, sudionici koji nisu završili ispitivanje do kraja (u nekim studijama u visokom broju) nisu bili uključeni u analizu.
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Description of the condition
Molluscum contagiosum is a viral skin infection most frequently encountered in children (Chen 2013). The infection is caused by the molluscum contagiosum virus, which is classified within the family of poxviruses (Poxviridae) (Buller 1991). The virus is assumed to be the only remaining poxvirus that specifically affects human beings (Chen 2013).
Infection follows after contact with infected people or contaminated objects (Chen 2013). 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. The lesions may itch (Rogers 1998).
In addition to the common form of benign skin tumours (mostly found in children), there is also a sexually transmitted variant of molluscum contagiosum that occurs on genital, perineal, pubic, and surrounding skin (Czelusta 2000). 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 immune deficiency (Gottlieb 1994; Mansur 2004). People with HIV infection are particularly prone to molluscum contagiosum; prevalence in this population has been reported to range from 5% to 18% (Hira 1988; Husak 1997; Matis 1987). The focus of this review was the common form of molluscum contagiosum only.
Molluscum contagiosum occurs worldwide. Previous reviews have reported that it as more frequent in geographic areas with warm climates, but this may be due to selective publication of local outbreaks (Olsen 2014). Infection is rare in children under the age of 1 year, typically occurring in the 2- to 5-year-old age group (Rogers 1998). The age of peak incidence is reported to be 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 incidence rate for children under 10 years of age was 6% (Sturt 1971). Population-based occurrence rates are scarce for high-income countries. 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 1878 an outbreak in an English school was reported involving 9 children (Liveing 1878). A recent meta-analysis of five cross-sectional surveys among children (age range 0 to 16 years) resulted in a pooled prevalence rate of 2.8% (95% confidence interval 0.0 to 5.9) (Olsen 2014).
In the USA, the estimated number of physician visits for molluscum contagiosum from 1990 to 1999 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 (Koning 1994; Relyveld 1988; Sturt 1971); 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 (Niizeki 1984; Postlethwaite 1967). 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.
The estimated incubation period varies from 14 days to 6 months (Sterling 1998). Lesions enlarge slowly and may reach a diameter of 5 to 10 mm in 6 to 12 weeks (Sterling 1998). After trauma (e.g. scratching) or spontaneously after several months, inflammatory changes result in the production of white fluid, crusting, and eventual destruction of the lesions. The duration of both 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.
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. A recent community cohort study in the UK, Olsen 2015, followed 306 children with molluscum contagiosum aged 4 to 15 years. Only 19% of the children were reported to have received treatment. Mean time to resolution was 13.3 months; 30% had not resolved by 18 months, and 13% had not resolved by 24 months.
Secondary bacterial infection can occur, and when severe can result in scarring. This must be distinguished from the milder inflammatory reactions that molluscum lesions show after a scratching or when they are starting to resolve spontaneously, which may prompt parents to take their child to the general practitioner thinking they have become infected (Highet 1992).
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 arrival (Beaulieu 2000; De Oreo 1956). Erythema annulare centrifugum (a widespread rash of red inflammatory rings) has also been reported (Vasily 1978). Chronic conjunctivitis and superficial punctate keratitis may likewise complicate lesions on or near the eyelids (Haellmigk 1966; Redmond 2004). The eczema and conjunctivitis diminish naturally 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 (Husak 1997). Only limited data are available on the course of the disease in this group of people.
Description of the intervention
In people without an immune deficiency molluscum contagiosum is a self limiting disease (Chen 2013). Therapy is often not necessary for recovery, and awaiting spontaneous resolution is an important management strategy (Brown 2006; Chen 2013; Jones 2007; Olsen 2015; Takemura 1983). 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 are means by which resolution of the lesions could be hastened (Sterling 1998).
Reasons to treat molluscum contagiosum include the following:
alleviating discomfort, including itching;
social stigma associated with many visible lesions;
limiting its spread to other areas of the body and to other people;
preventing scarring and secondary infection; and
preventing trauma and bleeding of lesions.
There are a large number of treatment options for molluscum contagiosum (see Table 1 for an overview). These treatment options can be divided into three major categories:
physical destruction of the lesions;
topical agents (i.e. those applied directly to the lesions); and
systemic treatment (i.e. those affecting the whole body).
In the past, many authors have recommended physical destruction as the preferred method for treatment of molluscum contagiosum (Smith 2002; Stulberg 2003; Williams 1991). Dermatology textbooks mention removal of the lesion with a sharp curette (curettage) or the application of liquid nitrogen (cryotherapy) as being simple and usually effective treatments (Lowy 1999; Sterling 1998). Gentle squeezing or pricking with a sterile needle are alternatively recommended destructive therapies (Berger 1996). Most of these therapies need 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 are also used (Hughes 2013; Metkar 2008; Saryazdi 2004; Silverberg 2000; Syed 1994; Weller 1999). In children, prior application of local anaesthetic cream may reduce the pain of treatment involving physical destruction or local inflammation (de Waard 1990; Rosdahl 1988), 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 a survey among paediatric dermatologists in the USA in 2008, respondents seemed to favour cantharidin, followed by imiquimod, watchful waiting, curettage, and cryotherapy (Coloe 2009). This differs from, for example, general practice in the Netherlands, where waiting for natural resolution is the most popular option (Van der Linden 2005). A more recent survey among physicians from various specialties in the USA showed that treatment preferences differed widely between specialties (Hughes 2013).
How the intervention might work
The working mechanism differs according to the type of treatment (Chen 2013). Curettage aims to remove the lesions entirely. Other techniques like pricking with a needle, cryotherapy, or pulsed-dye laser aim at damaging the lesion, which may in itself induce an immune response. Topical preparations such as podophyllotoxin, tretinoin, cantharidin, or potassium hydroxide are supposed to evoke a local inflammatory response. Application of phenol or trichloroacetic acid also aims to destroy the lesions. Another topical preparation, imiquimod, supposedly induces an immune response. Cimetidine is a systemic immune modulator. Antiviral agents, especially cidofovir, have been used both systemically and locally (Chen 2013).
Why it is important to do this review
Molluscum contagiosum is a common reason for consultation in family practice and dermatology. Many treatment options are available, some of which are painful and some that 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 which is the best option. We carried out this systematic review to evaluate treatment options for molluscum contagiosum.
Summary of main results
Twenty-two studies, with a total of 1650 participants, examined the effects of topical (20 studies) and systemic (2 studies) interventions. Altogether, we could extract evaluable data for 24 comparisons.
We found limited evidence of low quality from 11 comparisons for the short-term cure efficacy of the following topical treatments: cryospray when compared to 5% imiquimod; 10% potassium hydroxide compared to 5% imiquimod; 5% sodium nitrite co-applied with 5% salicylic acid compared to 5% salicylic acid alone; tea tree oil combined with iodine compared to tea tree oil or iodine alone; 10% Australian lemon myrtle oil compared to olive oil; and 10% benzoyl peroxide compared to 0.05% tretinoin. We found some evidence to suggest that 10% potassium hydroxide is more effective than saline; 5% solution of potassium hydroxide is favoured compared to 2.5% solution of potassium hydroxide; 10% povidone iodine solution plus 50% salicylic acid plaster is favoured compared to salicylic acid plaster alone; and homeopathic calcarea carbonica is favoured compared to placebo. We found no statistically significant differences for the other comparisons not including imiquimod.
The addition of three unpublished trial reports, with a total of over 800 participants, resulted in high- to moderate-quality evidence for the comparison of topical 5% imiquimod versus vehicle. We conclude that compared to vehicle, topical 5% imiquimod is probably no more effective in terms of clinical cure, makes little or no difference in terms of short-term improvement or local side effects, but appears to induce more application site reactions.
Overall, study limitations included lack of blinding, many dropouts, and no intention-to-treat analysis. Small study sizes resulted in broad confidence intervals and may have led to important differences being missed. None of the evaluated treatment options were associated with serious adverse effects, except for 5% imiquimod (severe application site reactions).
Although this update of our original review identified 11 new studies for inclusion, the overall conclusions have hardly changed, due to the small size of most of the studies and methodological shortcomings. We found no strong evidence either for or against the most commonly used treatment options for molluscum contagiosum. The evidence identified by this systematic review is therefore insufficient to propose any one intervention for molluscum contagiosum.
Overall completeness and applicability of evidence
Of the 11 trials added during the 2016 update, only three contributed to comparisons for which trials had been found in previous versions of this review. The other eight addressed new comparisons, thus increasing the fragmentation of the evidence. There remains an evidence gap regarding many promoted and used treatment options for molluscum contagiosum, with many interventions assessed by single, low-quality studies. For example, of the two studies that included a curettage arm (Hanna 2006; Machado 2010), the outcomes of Hanna 2006 were not suitable for inclusion in this review, and Machado 2010 was a very small study, with 50 participants divided over three study arms. We could include only two studies on cryotherapy (Al-Mutairi 2010; Handjani 2014).
Due to the small sample sizes of the low-quality, single-study comparisons that were included and for which no differences were found, it is possible that clinically relevant differences could be found if treatments would be evaluated in larger samples.
About half of the studies did not compare an active treatment to some sort of placebo, but rather compared two active treatments. This implies that for these interventions, the magnitude of benefit compared to placebo or doing nothing is unclear.
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 measured in most of the studies we found, or not at all; these included recurrences, and, especially, spread to other people and quality of life.
We initially 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 might favour the first type of treatment. For this update we have adapted our primary outcome to make it more manageable: short-term clinical cure (up to three months after start of treatment). A time point beyond one month after start of treatment for assessing cure was also suggested by Mc Cuaig 2011, commenting on the 2009 update of this review. An example of when time to cure since the last day of treatment is not appropriate is when treatment is continued until resolution of all lesions (e.g. Ohkuma 1990). Although no clear-cut solution seems available, and so far few trials have studied physical destruction (e.g. Hanna 2006; Machado 2010), it is advisable to always consider multiple outcome measures and also to take the burden of treatment into account.
We could perform a meta-analysis for only two comparisons: 5% imiquimod versus its vehicle and 5% imiquimod versus 10% potassium hydroxide.
We excluded studies on genital molluscum contagiosum and in participants with immune deficiency, so our conclusions do not apply to these participant groups, as the need for treatment is probably higher and may require different treatments.
Quality of the evidence
We included 22 studies with a total of 1650 participants in this update. Most of the included studies had small sample sizes, with a median study size of just over 30 molluscum participants, and only five studies with more than 100 participants. This impacted on our GRADE assessments. The small 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, most of the included studies used a control treatment that was not a placebo. Examples of comparator treatments in these studies were olive oil, saline, and alcohol, which may have had potential treatment effects. It was therefore difficult to compare the net effect of interventions due to the absence of a placebo group.
We could assign a low risk of bias for only a small proportion of items in the 'Risk of bias' table (Figure 2). 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, for example by constructing a funnel plot, due to the lack of directly comparable studies.
Notably, we judged five of the nine studies included in the 2016 update to be at low risk of bias (Coloe Dosal 2014; Eichenfield 2005; Markum 2012; Paller 2005a; Paller 2005b), suggesting a trend toward better study design or reporting, or both. However, with the exception of the three 'imiquimod versus vehicle' studies, most of the studies added during this update were small. The imiquimod studies overall had a low risk of bias (Eichenfield 2005; Paller 2005a; Paller 2005b; Theos 2004), therefore we did not downgrade the outcomes in Summary of findings for the main comparison for this domain.
As most of the evidence included in this review was based on low-quality studies, we were unable to reach a robust conclusion regarding the objective of the review.
Potential biases in the review process
Despite conducting a thorough search, we cannot be certain that we did not miss relevant randomised trials. One study is ongoing, and several others are awaiting classification and have not yet been incorporated into the review. Given that 19 of the included studies were performed or published, or both after 2000, we expect more studies comparing treatments for molluscum contagiosum to be published in the coming years.
We made several amendments to the original protocol, some of which were 'data-driven' in the sense that we encountered situations that we had not expected when we developed the protocol. This may have introduced bias.
Agreements and disagreements with other studies or reviews
At the time of the 2009 update of this review, we had found one other systematic review (Schmitt 2008). This review included six randomised trials, all of which were also included in our review. The conclusions of this review were similar to ours. During the 2016 update, we identified a new partly systematic (they described their databases, search strategy, and search date, but did not select studies or extract data in couples, did not state clear inclusion criteria, and did not assess risk of bias) review (Chen 2013), which addressed not only epidemiology, virology, and immunology of molluscum contagiosum, but also clinical management. They summarised the findings of the previous version of this review (Van der Wouden 2009), and mentioned three new trials (Al-Mutairi 2010; Köse 2013; Seo 2010), the first two of which have been included in this update, and the last which is awaiting assessment. They concluded that no evidence-based consensus has been reached on which is the best treatment for molluscum contagiosum in people without immune deficiency.
The cure rates found in the non-randomised study by Weller 1999 for physical expression and phenol ablation (75% and 77% of lesions, respectively, after one month) compare favourably to the 23% of children found cured in the Japanese cohort study on the natural history of the disease (Takemura 1983).
In the vehicle group of the 3M studies, clearance rates were 12% within 3 months; 27% after 3 to 6 months; and 40% beyond 6 months. Another, more recent cohort study from the UK (Olsen 2015), where only a small proportion of children were reported to have received treatment, found somewhat lower cure rates: around 10% after 6 months; 40% after 12 months; 75% after 18 months; and 80% after 24 months. Comparing these figures, 'vehicle' seems to work better than no treatment at all.
The authors thank Marjolein Berger, Chris Butler, Sanjay Gajadin, Jack Menke, and Marjolein Tasche for their involvement in writing previous versions of our review. The authors would also like to thank Adrie Hollestein, Ken Katz, Daan Muris, Kazutomo Ohkuma, Anthony 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. Derya Uçmak kindly sent us their paper. 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 (Takemura 1983), and Taixiang Wu for interviewing Dr He on details of her study design (He 2001). We thank Alireza Firooz for assessing the paper Salmanpour 2006, and Susheera Chatpoedprai for providing additional information on their study (Chatproedrai 2007). Clemens van Ede (at that time medical director of Meda Pharma BV, Netherlands) kindly provided the trial reports of the three unpublished 3M studies (Eichenfield 2005; Paller 2005a; Paller 2005b).
For the current update of this review, the Cochrane Skin editorial base wishes to thank Bob Boyle, Cochrane Dermatology Editor for this review; Matthew Grainge, Statistical Editor; Ching-Chi Chi, Methods Editor; the clinical referees, Paul Martin and Hywel Williams; and the consumer referee, Jack Tweed; as well as Lisa Winer, who copy edited the review.
Contributions of authors
JCvdW was the contact person with the editorial base, co-ordinated contributions from the coauthors, and wrote the final draft of the review.
SK, EJK, RvdS, and JCvdW screened papers against the eligibility criteria.
JCvdW obtained data on ongoing and unpublished studies.
SK, EJK, RvdS, and JCvdW appraised the quality of papers.
SK, EJK, RvdS, and JCvdW extracted data for the review and sought additional information about papers.
JCvdW and EJK entered data into Review Manager 5.
JCvdW and EJK analysed and interpreted data.
JCvdW worked on the Methods section.
All review authors commented on draft versions of this update.
SK drafted the clinical sections of the Background and responded to the clinical comments of the referees.
JCvdW responded to the methodology and statistics comments of the referees.
AS was the consumer coauthor and checked the review for readability and clarity, as well as ensuring outcomes were relevant to consumers.
JCvdW is the guarantor of the update.
This project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Skin Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.
Differences between protocol and review
The title of the published protocol was inadvertently left as 'Interventions for molluscum contagiosum in children', although a decision had been made not to restrict the review to children.
Differences between the protocol and the current update
For differences between other published versions, please see the 'Differences between protocol and review' sections within the original publications.
Objectives: In the protocol, we had planned to assess the effects of treatments, but in this and the previous updates we broadened this to include management strategies because waiting for natural resolution is a recognised option for dealing with molluscum contagiosum. We amended the text from that which was in the protocol to make our objectives more clear.
Types of studies: In the protocol, we said that "studies should compare one or more treatments with another, with placebo, or with no treatment (waiting for natural response)"; we removed this sentence in this and previous updates because it refers to comparisons rather than studies.
Types of interventions: We had planned to include randomised trials of all treatments for molluscum contagiosum, but narrowed this to include only treatments aimed at eradicating molluscum contagiosum lesions, and excluded studies on other aspects of the treatment of molluscum contagiosum, for example on reducing pain in the studies that assessed the effect of using an analgesic EMLA (eutectic mixture of local anaesthetics) cream before the actual intervention took place. This was because the analgesic was not used to eradicate the molluscum lesions.
Primary outcomes: We decided that our original choice for 'short-term clinical cure' of one month was not realistic, and therefore changed it to three months. We have also clarified our primary outcome to make it more manageable: short-term clinical cure (up to three months after treatment). (Please see Overall completeness and applicability of evidence for a more detailed description of why we felt the original choice was not realistic.) We also deleted the term 'elevated' in the description, as we felt it was unnecessary and could possibly cause confusion, the implication being that there are elevated and non-elevated forms of the lesion.
Where included studies used the term 'complete clearance' or 'free of lesions' or 'cured or > 90% cleared', we classed these as our primary outcome 'short-term clinical cure (up to three months after start of treatment)' or our secondary outcome 'medium- and long-term cure (after three months and up to six months, and after six months, respectively)'. Where studies have referred to 'partial clearance', we took this to mean our secondary outcome 'improvement'.
Secondary outcomes: We did not initially specify the outcome 'disease-related quality of life' in the protocol, but added it afterwards as we considered it to be a relevant additional measure.
We also added 'short-, medium-, and long-term improvement (including cure, intervals as above)' as a secondary outcome as we considered it to be important. For this outcome we combined 'improvement' and 'cure' (even though cure alone was a seperate outcome) because 'improvement' would be hard to interpret without also including those who were cured. For example: suppose in group A, 30% were cured and another 20% improved. In group B, 40% were cured and 10% improved. Comparing improvement rates between A and B (20% versus 10%) is misleading, whereas combining cure and improvement (50% versus 50%) is not.
Electronic searches: We expanded the number of trial registries that we planned to search when we became aware of the existence of these registries and in line with current Cochrane Skin practices. For similar reasons, we added Google as an additional electronic search strategy.
Selection of studies: If a randomised controlled trial included a variety of skin diseases, of which one was molluscum contagiosum, the number of molluscum participants needed to be at least five in the active treatment and placebo groups in order to reduce the role of extremely small studies. We added this criterion after the protocol was approved when we found a study that included 10 molluscum participants with a 9:1 distribution over the two treatment groups (Caballero 1996). The criterion also applied to Manchanda 1997a.
Selection of studies: If the setting of the study was not explicitly mentioned in the text, we assumed it to be carried out at the affiliation of the first author. Also, if the full text of a study was not available, we considered published abstracts for this update, as we have done this for previous versions of the review.
Assessment of risk of bias in included studies: In this update, we assessed each study using Cochrane's 'Risk of bias' tool (Higgins 2011), as this is now required. Also items (5), (6) and (7), which differed from the original protocol or were absent, were added or amended for the 2009 update as recommended. In previous versions of this review, items (3) and (4) were combined. For the 2016 update we further clarified how we decided what constituted an 'adequate' assessment and therefore low risk of bias.
Measures of treatment effect: Following the recent Cochrane Skin Group recommendations, we decided post hoc to re-analyse results from individual studies with borderline significance and with low numbers of events (fewer than 10 in total) or a total sample size of less than 30, using Fisher’s exact test. The resulting P value was leading in interpreting the results.
Data synthesis: We had planned to express dichotomous results as odds ratios, but changed this to risk ratios and as a number needed to treat where appropriate because these are easier for most readers to understand. We decided to report numbers needed to treat only for comparisons with more than one study and only in the case of statistically significant differences, the latter because numbers needed to treat for differences that are statistically not significant produce large and uncertain confidence intervals.
When the same comparison between two interventions was made in more than one study, and studies appeared to have been executed in similar groups and settings, we planned to use statistical tests for homogeneity between studies. In those studies where the available data were sufficiently homogenous and where a pooled estimate of the treatment effect made sense, we planned to conduct a meta-analysis. However, we could not implement these plans in most cases due to lack of data.
Assessment of reporting biases: Subsequent to the protocol, we aimed to assess reporting bias by comparing the published trial publications with the study protocol, but no protocols were available.
Unit of analysis issues: In our methods we planned to use special analytic techniques for paired (split-body) designs; however, we were unable to do this as the paired data were not available to us.
Dealing with missing data: Although this was not specified in the protocol, we considered participants who dropped out or were lost to follow-up as treatment failures.
Unit of analysis issues/Assessment of heterogeneity/Sensitivity analysis: We had planned analyses not documented in the protocol, including the use of sensitivity analyses to examine the effects of excluding studies with lower reported methodological quality, as well as how to analyse cross-over trials and within-participant designed trials. However, we did not undertake these analyses because of the small number of studies for each comparison.
Sensitivity analysis: We planned to use sensitivity analyses to examine the effects of excluding studies with high risk of bias. However, we did not undertake these analyses because of the small number of studies for each comparison.
Summary of findings: We developed 'Summary of findings' tables subsequent to our protocol. We have produced one for this update.
Quality of evidence: We used GRADE to assess the quality of evidence for each primary outcome and key secondary outcomes.