Curettage is a simple and relatively inexpensive procedure, with the added advantage that the tissue removed can be kept for histopathological analysis in case of diagnostic doubt.11 EMLA cream, a eutectic mixture of local anesthetics (2.5% lidocaine and 2.5% prilocaine), is frequently used in children to ameliorate the pain caused by the procedure, although its application on MC lesions can cause local, self-resolving purpuric reactions12,13 (Fig. 2). The risk of systemic toxicity should also be considered if EMLA is applied to a large area, particularly in infants less than 3 months old14 (Table 2). Curettage is probably one of the most effective methods. A retrospective clinical study of 1879 pediatric patients found that 70% were cured after a single treatment, 26% required 2 treatments, and only 4% required 3 treatments.15 Satisfaction was high (97% in children and parents). A randomized, controlled trial comparing the efficacy of curettage, cantharidin, salicylic acid with glycolic acid, and imiquimod found that curettage was the most effective therapy, resulting in complete resolution in 80.6% of patients with no recurrences after 6 months of follow-up.16 Disadvantages of curettage include the need for local anesthesia, potential pain and bleeding, and the risk of scarring.17

Figure 2.

Purpuric reaction to topical application of EMLA (eutectic mixture of local anesthetics) cream and occlusion for 1 hour.

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The umbilicated nucleus of the lesion can be manually removed using the hands or any one of a variety of instruments, including a scalpel, lancet, insulin needle, slide, or forceps (Fig. 3). The resulting scarring is similar to that caused by curettage. This technique is of particular interest as it is simple and fast and can be learned by patients, family members, and caregivers and therefore performed at home.11

Figure 3.

Manual expression of molluscum bodies with the fingers. A, The lesion is squeezed between 2 fingers. B and C, A whitish molluscum body is extruded. C, Tissue damage is minimal.

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Trichloroacetic acid causes tissue destruction by immediate chemical coagulation and superficial necrosis.18 It is used at concentrations of 20% and 35% and applied repeatedly on the center of the lesion until a white, frost-like covering forms. In a review of pediatric cases of facial MC treated with topical trichloroacetic acid, no irritation or marked pigmentary alterations were described, and patients reported only mild stinging during applications, which produced good clinical results.19 Adverse effects include pruritus in the treated area, irritation of the surrounding skin, ulceration, and scarring.18

Salicylic acid is a keratolytic agent sold at concentrations of 10% to 30%. A randomized controlled trial of treatment with 10% potassium hydroxide (KOH) or the combination of salicylic acid and lactic acid at 16.7% in 26 MC patients aged 2 to 12 years found no significant differences between groups after 6 weeks.20 Side effects included irritation, pruritus, a burning sensation, and peeling of the skin.

Hydrogen peroxide (HP) is a powerful oxidizing agent and antiseptic that can inactivate poxvirus in vitro.21 Treatment with HP, which is sold outside of Spain in a 1% cream, resulted in complete resolution of lesions in an 8-month-old patient with genital MC when applied at every diaper change for 1 week.22 The authors attributed the rapid resolution to greater exposure of the virus to HP because the skin was occluded by the diaper. In another study of 12 MC patients treated with 1% HP cream applied twice per day for 21 consecutive days, 67% attained full resolution without recurrence after 6 months of follow-up. Appropriate clinical trials are required to confirm the efficacy and safety of HP for the treatment of MC in children.

Cantharidin is a vesicant agent produced by the beetle Lytta vesicatoria.23 When applied to the skin, this phosphodiesterase inhibitor produces an intraepidermal blister that rarely leaves a scar owing to its superficial location.17 It is used at concentrations of 0.7% to 0.9%, and after application should be left in place for 2 to 4hours without occlusion and subsequently removed with soap and water.17 Other authors have proposed that in cases of resistant lesions cantharidin should be allowed to dry for 5 to 10 minutes and then occluded with adhesive tape.24 The treatment can be repeated at intervals of 1 to 4 weeks. In a retrospective study of 300 children with MC who were treated with cantharidin, a cure rate of 90% was achieved with an average of 2.1 treatments.18 The treatment itself is painless, but within 24 to 48hours painful blisters form, bringing the added risk of secondary superinfection. Cases of lymphangitis with lymphedema following cantharidin treatment have also been reported.25 Given these risks, cantharidin is not recommended for MC of the face or anogenital region.16

Imiquimod, an agonist of toll-like receptor 7, binds to this receptor, activating the innate immune response and inducing the synthesis of interferon-α, interleukin (IL)-1, IL-5, IL-6, IL-8, IL-10, and IL-12, and IL-1 receptor antagonist, among other factors. Imiquimod's antiviral and antitumor effects are mediated by both the adaptive and innate immune systems.33 It is available in a 5% cream to be applied at night, left for 8hours, and rinsed off in the morning. Some authors recommend daily application while others suggest 3 treatments per week.34 In one study in which children with MC were treated 3 times per week for 16 weeks with 5% imiquimod cream, complete resolution of MC was observed in 69%.35 The most frequent local adverse effects were erythema, pruritus, stinging, and pain, which in some cases was intense (Fig. 4).

Figure 4.

Irritation caused by the application of topical imiquimod on the right forearm.

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Oral cimetidine is an antagonist of H2 histamine receptors. It exerts immunomodulatory effects by stimulating delayed hypersensitivity. In a clinical study of 13 children of less than 10 years of age who were treated with 40mg/kg of oral cimetidine once per day for 2 months, complete lesion resolution was observed in 9 of 13 patients.36 The authors concluded that cimetidine was an easy to apply, effective, and painless alternative for treating facial, widespread, or recurrent MC in immunocompetent children. However, in a double-blind trial comparing placebo treatment with oral cimetidine (35mg/kg) administered once per day for 12 weeks in MC patients aged 1 to 16 years, no statistically significant differences were observed between the placebo and treatment groups.37 Based on this finding, the authors proposed that the efficacy observed in other studies may in fact be the result of spontaneous lesion resolution. Side effects of oral cimetidine are rare but include nausea, diarrhea, rash, and dizziness.36

Candidin, a substance derived from the purified extract of Candida albicans, is usually used to treat warts38 but has been proposed as a treatment option for MC.39 It is administered intralesionally either undiluted or at a concentration of 50% in lidocaine. The dose administered corresponds to 0.2 to 0.3mL of the antigen. In one retrospective study of 29 MC patients under the age of 17 who were treated with 0.3mL of intralesional candidin the global response rate was 93%, and complete and partial responses were observed in 55% and 37.9% of patients, respectively.40 Most side effects were minimal, but pain at the site of injection was experienced by 4 patients. In another retrospective review of 25 MC cases treated with intralesional candidin, complete resolution was observed in 14 (56%) cases, a partial response in 7 (28%), and no clinical improvement in 4 (16%).39 The advantages of immunotherapy in the treatment of MC include the induction of a memory immune response to MC, the potential to induce a generalized response that leads to resolution of untreated lesions in anatomically distant sites, and the lack of adverse effects.40 However, candidin, which is not commercially available in Spain, is scarcely used in clinical practice.

Silver nitrate is prepared with 0.2mL of a 40% aqueous solution of silver nitrate and 0.05g of flour. This semitransparent mixture is placed in the center of the lesion. After 24hours a dark crust begins to appear, and after about 14 days the MC lesion falls off. Treatment of 389 consecutive MC patients with 40% silver nitrate resulted in a cure rate of 97.7% and caused no scarring.41 This simple, inexpensive procedure is painless and causes few adverse reactions such as pain, stinging, erythema, chemical burns, or residual hyperpigmentation.42

Cidofovir is a nucleotide analogue of deoxycytidine monophosphate. Although its mechanism of action remains unclear, it is known to inhibit viral DNA polymerase, therefore blocking the synthesis of viral DNA. Cidofovir can be administered intravenously (5mg/kg/wk for 2 weeks followed by 5mg/kg once every 2 weeks) or topically (1%–3% cream or gel, applied daily).43 Several studies have described the successful use of intravenous or topical cidofovir for MC resistant to other treatments.44 However, this drug is expensive and further studies are required to determine its efficacy and safety in children.

Because MC is benign and self-limiting, a wait-and-see approach is reasonable. The time to resolution of MC varies. In a prospective community cohort study the average time to resolution of MC lesions in 306 British MC patients aged 4 to 15 years was 13.3 months.50 Thirty percent had not resolved at 18 months, and 13% remained unresolved at 24 months. However, many parents will not accept an indeterminate estimate of time to resolution and fear the potential risk of spread or transmission to other children.23 Moreover, in some cases the disease can be uncomfortable or stigmatizing. One survey found that parents were twice as likely as their children with MC to express significant concern about the disease.6 Parents’ concerns related to the clinical manifestations of MC (scarring, spread, itching, and pain) and the discomfort caused by available treatment methods. However, the same study found that infection did not significantly affect daily activities, quality of life, or individual productivity in school.