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Monday, October 26, 2015

MOLUSCO CONTAGIOSO / POX VIRUS . C.A. CENTRO MEDICO DE CARACAS / Molluscum Contagiosum










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Dr. Carlos E. Mijares, former fellow in Allergy / Immunology, pediatrics University of Kansas, USA


Molluscum contagiosum
Disclosures: Stuart N Isaacs, MD Nothing to disclose. Martin S Hirsch, MD Nothing to disclose. Moise L Levy, MD Grant/Research/Clinical Trial Support: Anacor [atopic dermatitis (investigational drug)]; Stiefel/GlaxoSmithKline [psoriasis (calcipotriene foam)]. Consultant/Advisory Boards: Galderma [acne (adapalene/benzoyl peroxide)]; Anacor [atopic dermatitis (investigational drug)]; Promius [atopic dermatitis (investigational drug)]. Patent Holder: Incontinentia pigmenti (NEMO gene mutations). Ted Rosen, MD Consultant/Advisory Boards: Anacor [Onychmycosis (Tavaborole)]; Valeant [Onychmycosis (Efinaconazole)]; Leo [Actinic keratosis]. Abena O Ofori, MD Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2015. | This topic last updated: Oct 07, 2015.
INTRODUCTION — Molluscum contagiosum is a poxvirus that causes a chronic localized infection, consisting of flesh-colored, dome-shaped papules on the skin of an infected individual. The epidemiology, clinical features, diagnosis, and management of molluscum contagiosum will be reviewed here.
VIROLOGY — Molluscum contagiosum is a member of the poxvirus family but is in a different genus from the orthopoxviruses (variola, vaccinia, and monkeypox viruses) discussed separately (see "The epidemiology, pathogenesis, and clinical manifestations of smallpox" and "Vaccinia virus as the smallpox vaccine" and "Monkeypox"). Molluscum contagiosum causes a chronic localized infection with small papules on the skin of an infected individual in contrast to the acute, sometimes fatal, disease induced by smallpox. Similar to the virus that causes smallpox, the only known host is humans.
Information about molluscum contagiosum at the molecular level has been hampered by the inability to grow the virus in standard cell culture or in an animal model of infection. While there are reports of some success in growth using human foreskin xenograft fragments [1], a major advance in understanding the biology of the virus came when the entire 190,000 base pair genome of the molluscum contagiosum virus was sequenced [2,3].
Like variola and vaccinia viruses, molluscum contagiosum replicates in the cytoplasm of cells, and thus, it is not surprising that more than one-half of the genes are similar to those found in variola and vaccinia viruses. However, since the diseases induced are quite different [4], it also is not surprising that many genes found in variola and vaccinia are not present in the molluscum contagiosum genome [2,3]. Molluscum contagiosum contains many unique genes that encode proteins responsible for novel host defense mechanisms; these mechanisms inhibit the host inflammatory and immune responses to the infection [5-9].
EPIDEMIOLOGY — Molluscum contagiosum infection has been reported worldwide. Although four distinct genotypes have been identified, genotype 1 predominates and represents 90 percent of cases in the United States [10]. A population-based Australian seroepidemiology study in 357 people revealed an overall seropositivity rate of 23 percent [11]. The data also indicated that very mild or subclinical cases may be more common in the general community than previously suspected.
It is estimated that fewer than 5 percent of children in the United States have clinical evidence of molluscum contagiosum infection [10]. The number of cases in adults has varied over time. In the 1980s, the number of molluscum contagiosum cases increased, apparently as a result of the acquired immune deficiency syndrome (AIDS) epidemic [12]; however, since the introduction of highly active antiretroviral therapy (HAART), the number of molluscum contagiosum cases in AIDS patients has decreased substantially [13].
RISK FACTORS — Molluscum contagiosum is a common disease of childhood. The disease also occurs in healthy adolescents and adults, often as a sexually transmitted disease or in relation to participation in contact sports [10]. Molluscum contagiosum is also associated with immunodeficient states. It can occur in the setting of underlying cellular immunodeficiency, such as occurs in inherited immunodeficiencies [14], during human immunodeficiency virus (HIV) infection, or following treatment with immunosuppressive drugs.
Although it has been proposed that atopic dermatitis is a risk factor for molluscum contagiosum (picture 1F), data conflict on the relationship between these diseases. An increased risk is suggested by studies that report prevalence rates for atopic dermatitis between 18 and 45 percent among patients with molluscum contagiosum, rates that exceed the estimated prevalence of atopic dermatitis in the general pediatric population (10 to 20 percent) [15]. It is theorized that the relative suppression of T-helper cell type 1 responses in acute skin lesions of atopic dermatitis could contribute to a predisposition for molluscum contagiosum in the atopic dermatitis population.
In contrast to the assertion that atopic dermatitis is a risk factor for this infection, a nursery school-based study of over 1100 children in Japan failed to find a statistically significant increase in molluscum contagiosum among children who had a history of atopic dermatitis compared with children without atopic dermatitis (odds ratio 1.64, 95% CI 1.00-2.68) [16]. Thus, the relationship between atopic dermatitis and molluscum contagiosum remains uncertain.
TRANSMISSION — Like many viruses in the poxvirus family, molluscum contagiosum is spread by direct skin-to-skin contact and thus can occur anywhere on the body. The virus can be transmitted via autoinoculation by scratching or touching a lesion. For example, if the lesions develop on the face, shaving may spread the virus. The only known host for molluscum contagiosum is humans.
Infection can also be spread via fomites on bath sponges or towels or through skin contact during participation in contact sports [10]. An association of molluscum contagiosum with swimming pool use also has been reported [17]. When it occurs in the genital region in sexually active individuals, molluscum contagiosum is classified as a sexually transmitted disease. In contrast, autoinoculation, rather than sexual contact, is responsible for most anogenital lesions in children [18].
Estimates for the incubation period of the virus vary from one week to six months, but it is typically characterized as being between two and six weeks [17].
CLINICAL FEATURES — The molluscum contagiosum virus causes a chronic localized infection characterized by firm, dome shaped papules on the skin (picture 1A-F). Lesions are often 2 to 5 mm in diameter, with a shiny surface and central indentation or umbilication. Occasionally, the growths can be polypoid with a stalk-like base. Pruritus may be present or absent, and lesions sometimes become visibly inflamed.
Molluscum contagiosum may appear anywhere on the body except the palms and soles. The most common areas of involvement include the trunk, axillae, antecubital and popliteal fossae, and crural folds. Lesions on the eyelid can cause conjunctivitis (picture 2A-B) [19]. Oral mucosal involvement is rare [20]. Sexually transmitted molluscum contagiosum typically involves the groin, genitals, proximal thighs, and lower abdomen. In HIV-infected and other immunocompromised patients, lesions can be large (aka giant molluscum) and widespread (picture 3A-B).
ASSOCIATED CLINICAL FINDINGS
Molluscum dermatitis — Molluscum dermatitis, which is characterized by the development of eczematous patches or plaques surrounding molluscum contagiosum lesions, is a common phenomenon (picture 4). Estimates of the proportion of patients with molluscum who develop molluscum dermatitis have ranged from 9 to 47 percent [15].
Whether the use of topical corticosteroid therapy for molluscum dermatitis impacts the prognosis of molluscum contagiosum is unclear. Although there is some concern that local immunosuppression from topical corticosteroids could inhibit clearance of the infection, this has not been proven [21,22]. On the other hand, it is conceivable that untreated molluscum dermatitis could contribute to spread of the infection through scratching.
A short course (eg, up to two weeks) of a low or medium potency topical corticosteroid (table 1) can be used to treat sites of molluscum dermatitis in patients in whom the condition is pruritic. Emollients may be used for the management of asymptomatic patients [22].
Inflamed lesions — Inflamed molluscum contagiosum, which is characterized by erythema and swelling of individual lesions, is a clinical finding that may portend a higher likelihood of impending clinical improvement [15,23]. In a retrospective study of 696 children with molluscum contagiosum, children with inflamed lesions were less likely to develop an increase in the number of lesions over the course of three months than patients who had neither inflamed lesions nor molluscum dermatitis [15]. In a case series of seven children with inflamed molluscum, the duration from onset of inflammation to resolution ranged from three weeks to five months [23]. Inflamed molluscum should not be mistaken for secondary bacterial infection. Antibiotic treatment is not needed.
Other — Gianotti-Crosti syndrome (also known as papular acrodermatitis) is a pruritic inflammatory skin condition that may occur in association with viral infections in children (picture 5). The face, buttocks, and extremities are common sites for lesion development. (See "Gianotti-Crosti syndrome (papular acrodermatitis)".)
Gianotti-Crosti like eruptions have been reported in patients with molluscum contagiosum. In one large retrospective study, this phenomenon was diagnosed in 5 percent [15]. Gianotti-Crosti like reactions may portend a higher likelihood of forthcoming clinical improvement [15].
DIAGNOSIS — The diagnosis of molluscum contagiosum is usually made by the characteristic appearance of the lesions (picture 6). When necessary, histologic examination can confirm the clinical diagnosis. Hematoxylin and eosin staining of a molluscum contagiosum lesion typically reveals keratinocytes containing eosinophilic cytoplasmic inclusion bodies (also known as molluscum bodies or Henderson-Paterson bodies) (picture 7) [24].
Dermoscopic examination can be useful for supporting a clinical diagnosis of molluscum contagiosum. Visualization of a central umbilication with polylobular, white to yellow amorphous structures is typical [25,26]. A peripheral crown of radiating or punctiform vessels is also present [27].
Although usually not indicated, electron microscopy of biopsies demonstrates typical brick-shaped poxvirus particles. Electron microscopy can also identify infected cells that appear normal on light microscopy [28].
Skin lesions due to cryptococcosis, histoplasmosis, or Penicillium marneffei infection may resemble molluscum lesions (picture 8A-E) [29]. The possibility of these disorders should be considered in immunosuppressed patients. Other lesions that may be mistaken for molluscum contagiosum include flat warts, condyloma acuminatum, condylomata lata (picture 9), pyogenic granuloma (picture 10), adnexal tumors, Langerhans cell histiocytosis (picture 11), basal cell carcinoma (picture 12), and amelanotic melanoma. Skin biopsy is useful for distinguishing molluscum contagiosum from other disorders. (See"Pathogenesis and clinical manifestations of disseminated histoplasmosis" and "Cryptococcus neoformans infection outside the central nervous system", section on 'Nonmeningeal, nonpulmonary cryptococcosis' and "Epidemiology and clinical manifestations of Penicillium (Talaromyces) marneffei infection", section on 'Clinical manifestations'.)
NATURAL HISTORY — In immunocompetent patients, individual lesions usually spontaneously resolve within two months and the infection often clears completely within six to twelve months [18,23,30]. In a minority of cases, disease persists for three to five years [18,23,30]. Although scarring can occur after spontaneous resolution, most molluscum contagiosum lesions do not resolve with scars.
LABORATORY TESTS — Laboratory studies usually are not indicated in children with molluscum contagiosum. Sexually active adolescents and adults with genital lesions should be evaluated for the presence of other sexually transmitted diseases. Patients with extensive lesions should be tested for human immunodeficiency virus (HIV) infection, and the possibility of other immune system disorders should also be considered. (See "Screening and diagnostic testing for HIV infection" and "Approach to the child with recurrent infections".)
OVERVIEW OF MANAGEMENT — The self-limited nature of molluscum contagiosum and the paucity of evidence that definitively supports therapeutic intervention have led to debate over the need for treatment [31-34].
Decision to treat — Potential advantages of successful treatment include limitation of lesion spread to other sites, reduction of the risk of transmission to others, resolution of pruritus when present, and the prevention of scarring that can result from lesions that become inflamed, traumatized, or secondarily infected. Treatment may also reduce patient or parental psychological stress over the appearance of lesions. However, depending on the chosen therapy, treatment can be time consuming or can result in adverse effects such as pain, irritation, dyspigmentation, or scarring.
In general, adolescents and adults with sexually-transmitted molluscum contagiosum should be treated to avoid spread of the disease to others. Early treatment is also indicated in the setting of immunocompromised individuals, in whom infections can become severe.
For immunocompetent children with molluscum contagiosum, treatment is optional. One retrospective study utilizing a telephone survey and medical chart review found similar rates of molluscum contagiosum resolution among 46 treated and 124 untreated children; approximately 50 percent of children in both groups had complete resolution within 12 months [34].
We typically inform parents and guardians of the expected course of the disease without treatment and the potential adverse effects of each treatment option. When parents or guardians desire intervention, we proceed with therapy.
Prior to treatment, a full skin examination should be performed on patients with molluscum to identify all lesions. Incomplete treatment may result in continued autoinoculation and failure to achieve cure.
Periocular lesions — The destructive methods and topical agents reviewed below should not be utilized on lesions involving the ocular mucosa or eyelids. Patients with symptomatic ocular lesions should be referred to an ophthalmologist for management.
FIRST-LINE THERAPIES — Strong evidence for the efficacy of any treatment for molluscum contagiosum is lacking. A 2009 systematic review of randomized trials that investigated the efficacy of treatments for nongenital molluscum contagiosum in healthy individuals found insufficient evidence to conclude that any treatment was definitively effective [33].
Despite the absence of large placebo-controlled trials to support the efficacy of cryotherapy, curettage, and cantharidin, the rapid, clinically evident response associated with their use offers some support for their utility for the removal of individual lesions. The efficacy of podophyllotoxin is supported by data from a placebo-controlled randomized trial. Thus, when a trial of treatment is desired, we consider cryotherapy, curettage, cantharidin, and podophyllotoxin as first-line therapeutic options. The efficacy and safety of podophyllotoxin for molluscum contagiosum in young children have not been definitively established.
Cryotherapy — Liquid nitrogen is used to perform cryotherapy. A cotton-tipped swab dipped in liquid nitrogen and applied to individual lesions for 6 to 10 seconds can be used to perform this technique [18].
Cryotherapy was shown to be a rapidly effective therapy in a randomized trial (see 'Comparative studies' below) [35]. Treatment is often well tolerated in adolescents and adults; however, the pain associated with cryotherapy can limit its use in young children, particularly if multiple lesions are present.
Scarring and temporary or permanent hypopigmentation are potential adverse effects of cryotherapy. Hypopigmentation can be prominent in individuals with dark skin.
Curettage — Curettage involves the physical removal of molluscum contagiosum with a curette. The immediate resolution of lesions has led some clinicians to use this method as their preferred therapy for molluscum contagiosum [36].
In contrast to a randomized trial that found that more than 80 percent of patients were cured after a single session of curettage [36], a prospective study of 73 children and adults treated with curettage found that 42 out of 64 patients (66 percent) were not cured after a single session, and 25 out of 55 (45 percent) failed to clear after two sessions [37]. Risk factors for treatment failure included a high number of lesions and concomitant atopic dermatitis. (See 'Comparative studies'below.)
The discomfort and minor bleeding associated with this procedure can be disturbing for some children, and the possibility of the development of small, depressed scars should be discussed with patients or their guardians prior to proceeding. Treatment may be time-consuming due to the need to ease children's fears about the procedure. Topical anesthetics applied prior to curettage can reduce discomfort and facilitate therapy. (See "Topical anesthetics in children".)
Cantharidin — Cantharidin is a topical blistering agent that is commonly used for the treatment of molluscum [38]. Treatment should be performed by a clinician; patients should not be given cantharidin to apply at home. The expected response is the development of a small blister at the treatment site, followed by disappearance of the molluscum lesion and healing without scarring.
In a retrospective study of 300 children treated with cantharidin for molluscum, 90 percent of children had lesion clearance, and 8 percent demonstrated improvement [39]. On average, 2.1 clinician visits were necessary to achieve complete clearance. The parents of the patients appeared satisfied with treatment; 95 percent stated that they would be willing to have their child treated again with cantharidin.
Cantharidin is applied directly to lesions; the blunt wooden end of a cotton swab can be used for application. The site may be then covered, such as with a bandage, to avoid inadvertent spread of the vesicant to other areas. Cantharidin should be washed off with soap and water two to six hours after application or at the first sign of blistering [18]. Occasionally blistering can be exuberant, and it is reasonable to treat a small number of lesions at the first visit. The duration of application can be adjusted based upon the initial response.
Treatments can be repeated every two to four weeks until all lesions have resolved [39]. In general, treatment withcantharidin should be avoided on the face, genital, or perianal areas.
Common adverse effects include transient burning, pain, erythema, and pruritus [39]. Postinflammatory dyspigmentation may occur, but typically resolves over several months. While uncommon, scarring can occur as a consequence of cantharidintreatment [40].
Podophyllotoxin — Podophyllotoxin is an antimitotic agent that is commercially available as podofilox 0.5% (Condylox) in a solution or gel. The efficacy of podophyllotoxin was explored in a randomized trial of 150 males (ages 10 to 26 years); most lesions were located on the thighs or genitalia. Patients in the trial applied 0.5% podophyllotoxin cream, 0.3% podophyllotoxin cream, or placebo twice daily for three consecutive days per week [41]. Treatment was continued for up to four weeks. By the end of treatment, the superiority of 0.5% podophyllotoxin was evident; 92, 52, and 16 percent of patients in the 0.5% podophyllotoxin, 0.3% podophyllotoxin, and placebo groups were cured, respectively.
Local erythema, burning, pruritus, inflammation, and erosions can occur with the use of this agent. The safety and efficacy of podophyllotoxin for molluscum contagiosum have not been definitively established in young children.
OTHER INTERVENTIONS — Although topical therapies such as imiquimod and potassium hydroxide (KOH) have been used for the treatment of molluscum, sufficient data to support a recommendation for the use of these and several other treatments are lacking.
Imiquimod — Imiquimod is a topical immunomodulator that induces the local production of proinflammatory cytokines. Although favorable responses to imiquimod have been reported in uncontrolled studies and case series [42-44], the drug has not been proven more effective than placebo in randomized trials, suggesting that spontaneous resolution may account for some observations of efficacy. Because of the lack of clarity regarding the effect of imiquimod on molluscum contagiosum, we are unable to recommend the routine use of this drug for therapy.
Imiquimod did not appear to be effective in two large, unpublished randomized trials of children who were treated with imiquimod 5% cream or vehicle three times weekly for up to 16 weeks [45]. In the first study, complete clearance of molluscum occurred in 52 of 217 children in the treatment group (24 percent) versus 28 of 106 children in the vehicle group (26 percent). In the second trial, clearance occurred in 60 of 253 children (24 percent) and 35 of 126 children (28 percent) in the treatment and vehicle groups, respectively. A small, published, placebo-controlled randomized trial (n = 23) also was unable to demonstrate a benefit of imiquimod [46]. Although significantly more patients treated with imiquimod 5% cream (applied three times weekly for up to 12 weeks) achieved partial clearance by week 12 (defined as a ≥30 percent decrease in lesion count) than patients in the placebo group (67 versus 18 percent), the difference in the complete clearance rate (33 versus 9 percent, respectively) was not statistically significant. The small size of the trial may have contributed to the lack of statistical significance.
A few trials have compared imiquimod with other treatments for molluscum. In a small randomized trial, once weekly cryotherapy was associated with a faster rate of lesion clearance than imiquimod 5% cream applied five days per week, but a similar rate of complete cure was observed [35]. Trials that have compared imiquimod with other treatments are reviewed below. (See 'Comparative studies' below.)
Imiquimod is usually applied at night and washed off in the morning. Erythema and pruritus at application sites are common adverse effects [47]. Flu-like symptoms may also occur.
Potassium hydroxide — Potassium hydroxide (KOH), in concentrations of 5 or 10%, has been used for molluscum contagiosum [48-50]. Application frequency reported in the literature ranges from three times per week to twice daily.
In a randomized trial in which 20 children were treated with either 10% KOH or normal saline (applied twice daily until signs of inflammation), 7 out of 10 patients treated with KOH cleared completely (average time to clearance 54 days), while only 2 out of 10 in the placebo group were cured [48]. The difference between the two groups was not significant; thus, larger placebo-controlled randomized trials are necessary to evaluate the efficacy of this agent.
In a separate series of 20 children treated twice daily with 5% KOH in an aqueous solution, all patients cleared within six weeks [50]. Treatment with KOH also has been compared with other therapies for molluscum in randomized trials [51-53]. (See 'Comparative studies' below.)
Stinging or burning sensations often accompany application of KOH [51], and may be reduced with the use of the 5% concentration [49]. Temporary dyspigmentation is another potential adverse effect of this therapy.
Salicylic acid — Salicylic acid is a widely available keratolytic that has been used in the treatment of molluscum contagiosum. In a randomized trial of 124 children, an agent containing salicylic acid 16.7% and lactic acid 16.7% (Duofilm) applied with a tooth pick at home three times per week was compared with three other treatments (see 'Comparative studies'below) [36]. Compared with curettage, patients treated with salicylic acid were more likely to return to the office, which they were instructed to do if lesions persisted. Adverse effects were frequent; 54 percent of patients treated with salicylic/lacticacid experienced side effects. Local irritation is common with the use of salicylic acid.
Use of salicylic acid in combination with sodium nitrite [54] or povidone iodine solution [55] has also been reported.
Topical retinoids — Tretinoin (0.5% cream, 0.1% cream, or 0.025% gel), adapalene, and tazarotene have been used for the treatment of molluscum [56-59]. The mechanism of action is thought to involve the induction of local irritation that damages the viral protein-lipid membrane [60]. Data on the efficacy of these agents are limited to reports of clinical experiences [56-59].
Treatment with topical retinoids can begin every other day and can be increased to twice daily as tolerated [18]. Application is discontinued once local erythema develops [18]. Irritation and xerosis are expected side effects. Topical retinoids should not be used during pregnancy.
Other topical agents — A paste containing 40% silver nitrate was reported to be effective in a series of 389 patients [61]. Topical phenol [62] and trichloroacetic acid [31,63] also have been used for molluscum contagiosum, but high risks for pain and scarring make these agents unfavorable options.
ZymaDerm is a nonprescription topical homeopathic agent that is marketed for the treatment of molluscum contagiosum. No published studies have evaluated the efficacy and safety of ZymaDerm for this indication.
Other physical interventions — Pulsed dye lasers have shown efficacy in case reports and small uncontrolled studies [64-70]. In a prospective study of 19 children treated with a 585 nm pulsed dye laser, a single treatment led to disease resolution in 84 percent of patients [64]. Use of topical anesthetics prior to pulsed dye laser treatment may help to reduce pain associated with laser therapy. Potassium titanyl phosphate (KTP) lasers [71], carbon dioxide lasers [72,73], and photodynamic therapy have also been used to treat lesions.
Additional physical interventions that have been reported in the treatment of molluscum contagiosum include electrodessication, manual extrusion of the central core by squeezing [62], removal with sterilized tweezers [74], needle penetration in combination with topical tretinoin [75], intralesional injection with Candida antigen [76], and topical 20 to 35%trichloroacetic acid [77]. The efficacy and safety of these interventions have not been studied in randomized trials.
Oral cimetidine — Cimetidine is an H2 antihistamine that has also been found to have immunomodulatory properties. Data conflict on the efficacy of this agent for molluscum contagiosum [78,79]. In a series of 13 children with molluscum contagiosum who had failed to respond to other therapies, treatment with cimetidine (40 mg/kg/day for two months) was associated with clearance of all lesions [79]. However, in a separate series of 14 children treated with cimetidine 40mg/kg/day, only four children cleared within three months, and seven children showed no improvement [78]. Three children who did not take cimetidine due to the taste of the medicine or treatment cost spontaneously improved within three months, raising questions about the efficacy of treatment. Additional studies are necessary to investigate the efficacy of cimetidine in the management of molluscum.
COMPARATIVE STUDIES — There are relatively few trials that compare the efficacy of treatments for molluscum. Examples of the available data include:
Multiple therapies – A randomized trial of 124 children (ages 1 to 16 years) compared the safety and efficacy of curettage with topical anesthesia, cantharidin 0.7% (applied for two to four hours), a combination product with 16.7% salicylic acid and 16.7% lactic acid (three times per week), and imiquimod 5% cream (three times per week) [36]. Ten lesions on each patient were treated according to protocol, and the remaining lesions on all patients were treated with curettage. Telephone follow-up was performed on days 7, 21, 84, and 180 and follow-up visits were scheduled for patients with residual lesions. Curettage required the fewest follow-up visits for resolution of all 10 lesions, with 81 percent of patients requiring only one visit. Cantharidin, salicylic/lactic acid, and imiquimod required only one visit 37, 54, and 57 percent of the time, respectively. Parent and patient satisfaction with treatment was highest in the curettage group (87 percent), followed by cantharidin (60 percent), imiquimod (45 percent), and salicylic/lactic acid (32 percent). Adverse effects were most common in the group treated with salicylic acid (53 percent of patients).
Imiquimod versus cryotherapy – Imiquimod (applied five days per week) was compared with cryotherapy (once weekly) in a randomized trial of 74 children with molluscum contagiosum [35]. Treatment with either regimen was continued until lesion resolution or for up to 16 weeks. Cryotherapy led to complete cure in all patients and more rapid resolution than imiquimod; the majority of children (26 out of 37; 70 percent) were cured within three weeks. In the imiquimod group, 34 of 37 (92 percent) achieved complete cure, with the majority (22 out of 37; 59 percent) clearing within six weeks. The difference in complete cure rates between the two groups was not statistically significant. However, adverse effects (pain, bullae, dyspigmentation, mild scarring) were more common in cryotherapy group.
Imiquimod verus KOH  Two randomized trials have compared the efficacy of imiquimod 5% cream and 10% potassium hydroxide (KOH). The trials did not find significant differences in efficacy.
In a randomized trial of 30 patients with molluscum contagiosum (ages 1 to 36 years), patients were treated with either agent three nights per week until lesion clearance or for up to 12 weeks [52]. Statistically significant reductions in lesion counts were observed in both groups, but a statistically significant difference in efficacy between the two treatments was not detected. In the trial, 8 out of 14 patients treated with imiquimod (57 percent) and 10 out of 13 patients treated with KOH (77 percent) achieved complete clearance. All patients who achieved complete responses cleared within eight weeks.
Imiquimod and 10% KOH were found to be equally effective for achieving disease clearance in another randomized trial in which patients (ages 2 to 32 years) were treated with either agent three times weekly; all lesions resolved within 12 weeks in 8 out of 18 patients given imiquimod (44 percent) and 8 out of 19 of patients given KOH (42 percent) [51]. Compared with imiquimod, KOH appeared to have a more rapid onset of action and a higher rate of adverse effects (56 versus 78 percent developed side effects). The most common side effects observed were erythema and crusting.
Cryotherapy versus KOH – Cryotherapy and KOH were similarly effective in a four-week trial in which 30 patients (ages 1 to 24) were randomly assigned to once weekly cryotherapy or twice daily applications of 10% KOH [53]. After four weeks, 14 of 15 patients in the cryotherapy group (93 percent) and 13 of 15 patients in the KOH group (87 percent) had complete clearance of molluscum lesions. Side effects of transient hyperpigmentation and hypopigmentation occurred in both groups.
IMMUNOCOMPROMISED PATIENTS — Immunocompromised patients can develop severe, persistent cases of molluscum contagiosum. Therapies that result in wounds, such as curettage, may be a less favorable option for immunocompromised patients because of an elevated risk for infection.
Successful treatment of severe, refractory molluscum contagiosum in immunocompromised patients with imiquimod has been reported in multiple patients [43,59,80-82]. Similar to the use of the drug in immunocompetent patients, imiquimod is usually applied three nights weekly. (See 'Imiquimod' above.)
In addition to the treatments above, immunocompromised patients with refractory disease have been treated with agents such as interferon alpha and cidofovir.
Interferon alpha — Immunodeficient children and adults have attained resolution of severe, refractory lesions with subcutaneous interferon alpha [83-85]. The use of intralesional interferon alpha has also been reported [86].
Influenza-like symptoms are common adverse effects of interferon therapy.
Cidofovir — Intravenous cidofovir [87-89] and topical cidofovir (1% or 3%) [88,90-93] have been used in immunocompromised patients with severe, refractory molluscum.
Renal toxicity is a significant concern with the use of systemic cidofovir. Local irritation and painful cutaneous erosions can occur after application of the topical form [92]. Due to the absence of a commercial product, preparation of topical cidofovir must be entrusted to a compounding pharmacy. The stability, bioavailability, and optimal dosing regimen of such extemporaneous mixtures are unknown.
HIV therapy — Recovery of immune function may result in improvement. In HIV-infected patients, there have been multiple reports of recalcitrant molluscum contagiosum lesions resolving only after initiation of effective antiretroviral therapy [13,94]. However, the development of molluscum contagiosum has also been reported in association with immune reconstitution inflammatory syndrome (IRIS) following antiretroviral therapy in patients with HIV infection [93]. (See "Immune reconstitution inflammatory syndrome".)
SCHOOL AND SPORTS — It is not necessary to remove children with molluscum contagiosum from daycare or school; however, care should be taken to reduce the risk of transmission to others. Lesions in areas that are likely to come in contact with others should be covered with clothing or a watertight bandage. Bathing with other children should be avoided and towels and sponges should not be shared.
Affected individuals do not need to be excluded from contact sports activities provided lesions can be covered with clothing or bandages. Individuals with molluscum contagiosum should not be restricted from the use of public swimming pools.
PREGNANCY — Molluscum contagiosum in pregnancy is not common and the vertical transmission rate is not known. Only a small number of cases of congenital transmission have been documented in the literature [95].
Since molluscum contagiosum is spread by direct contact, a woman with genital lesions at the time of a vaginal delivery could theoretically transmit molluscum to her newborn, as is seen with genital warts. However, studies that have examined the incidence of molluscum contagiosum in children reveal that it is extremely uncommon to find molluscum contagiosum in children under the age of one [96,97]. The lack of many cases in this age group may indicate that infants are protected by passive maternal antibodies or that the infection has a very long incubation period.
There are scant data regarding the management of molluscum contagiosum in pregnancy since it is uncommonly encountered. Due to the toxicity of the chemicals commonly used to treat molluscum contagiosum (eg, podophyllotoxin orimiquimod), we do not recommend their use during pregnancy. Other options include cryotherapy or curettage or no treatment, since molluscum contagiosum is a self-limited disease. Dressings to cover visible lesions during delivery (eg, Tegaderm) may be considered to avoid skin-to-skin contact and hopefully lessen the risk of transmission.
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SUMMARY AND RECOMMENDATIONS
Molluscum contagiosum is a poxvirus that causes localized skin infections. (See 'Virology' above.)
Molluscum contagiosum is commonly seen in children, but can also occur in adults. The virus is transmitted through direct skin contact or fomites. Molluscum contagiosum infection in the genital region may result from transmission during sexual activity. (See 'Epidemiology' above and 'Transmission' above.)
The incubation period for molluscum contagiosum is uncertain, but has been estimated to be between two and six weeks. (See 'Transmission' above.)
Molluscum contagiosum most commonly presents as single or multiple small, flesh-colored papules with central umbilication (picture 1A-F). Immunosuppressed individuals have an increased risk for larger lesions and more widespread disease (picture 3A-B). (See 'Clinical features' above.)
The diagnosis of molluscum contagiosum typically is based upon the clinical appearance of skin lesions. Biopsy can confirm the diagnosis when necessary. Histopathologic examination of a lesion of molluscum contagiosum reveals eosinophilic cytoplasmic inclusion bodies within keratinocytes (picture 7). (See 'Diagnosis' above.)
Molluscum contagiosum infection is usually self-limited in immunocompetent individuals, and electing not to treat is a satisfactory option. In general, molluscum in the genital region should be treated due to the potential for sexual transmission. (See 'Overview of management' above.)
Inflammation of molluscum is common and can be a sign of impending regression. Inflammation should not be mistaken for bacterial infection. (See 'Inflamed lesions' above.)
High quality data on the efficacy of treatments for molluscum contagiosum are limited. When a trial of treatment is desired, we suggest the use of cryotherapy, curettage, cantharidin, or podophyllotoxin over other therapies (Grade 2B). The use of cantharidin should be avoided in the genital area. The efficacy and safety of podophyllotoxin for molluscum contagiosum in children has not been definitively established. (See 'First-line therapies' above.)
Prominent hypopigmentation may result from treatment with cryotherapy in patients with dark skin. The risks and benefits of cryotherapy should be considered carefully in these patients. (See 'Cryotherapy' above.)
Imiquimod, potassium hydroxide (KOH), salicylic acid, and topical retinoids have also been used for the treatment of molluscum contagiosum. However, data in support of the efficacy of these treatments are insufficient for a recommendation for the routine use of these therapies. (See 'Other interventions' above.)
The efficacy of cimetidine for molluscum contagiosum is uncertain. Cimetidine should not be used as a first-line therapy for molluscum contagiosum. (See 'Oral cimetidine' above.)
Immunocompromised patients are at risk for extensive and persistent disease. Improvement in molluscum contagiosum may occur in patients with human immunodeficiency virus (HIV) infection after the initiation of antiretroviral therapy. (See 'Immunocompromised patients' above.)
Children with molluscum contagiosum should not be excluded from daycare or school. Lesions should be covered with clothing or a bandage to reduce the risk of transmission to others. (See 'School and sports' above.)
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