【文献Abstract】みずいぼ（伝染性軟属腫）の治療

〈要点〉

・伝染性軟腫症の治療の有効性に関する強力なエビデンスはない。

・凍結療法、掻爬術などは有効性を裏付ける大規模なプラセボ対照試験はないが、臨床的な経験上有用性についてはある程度支持されている。ポドフィロトキシン（尖圭コンジローマの治療薬）の有効性は、プラセボ対照ランダム化試験のデータによって裏付けられている。そのため、治療が望まれる場合、凍結療法、掻爬術、ポドフィロトキシンを第一選択の治療選択肢となる。ちなみに幼児の伝染性軟腫症に対するポドフィロトキシンの有効性と安全性は明確に確立されていない。

・イミキモド（尖圭コンジローマの治療薬）や5～10％の濃度の水酸化カリウム（KOH）などの局所療法が伝染性軟腫症の治療に使用されてきたが、これらおよび他のいくつかの治療法の使用に関する推奨事項を裏付ける十分なデータが不足している。

・サリチル酸（スピール膏）—サリチル酸は、伝染性軟腫症の治療に使用されてきた広く利用可能な角質溶解剤。 124人の子供を対象としたランダム化試験では、サリチル酸16.7％と乳酸16.7％を含む薬剤を自宅で週に3回つまようじで塗布し、他の3つの治療法と比較したところ、患者の54％が治療したが　副作用も多くみられた。

〈雑感〉

子供が1年前から水いぼがあり、周囲の発赤が強い。基本的には経過観察でいいかなと、外来の子供たちにもそのように指導していたが、実際自分の子供がかかるとかわいそうで治したくなってしまう。。機械的に切除するのは嫌がるので、スピール膏など試してみてもよいか…？

〈文献〉

Molluscum contagiosum
Author:Stuart N Isaacs, MD

2021 UpToDate.This topic last updated: Jan 24, 2020.

FIRST-LINE THERAPIES
Strong evidence for the efficacy of any treatment for molluscum contagiosum is lacking. A 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 [19]. (See "Minor dermatologic procedures", section on 'Cryotherapy (cryosurgery)'.)

Cryotherapy was shown to be a rapidly effective therapy in a randomized trial (see 'Comparative studies' below) [34]. 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 the molluscum contagiosum lesion with a curette. The immediate resolution of lesions has led some clinicians to use this method as their preferred therapy for molluscum contagiosum [35].

Support for the use of curettage comes from a retrospective study that found that 70 percent of 1878 children treated with curettage were cured after a single treatment session [36]. In addition, a trial in which 124 children with molluscum contagiosum were randomly assigned to one of four treatment modalities found that 81 percent of 31 children treated with curettage were cured after a single session [35]. (See 'Comparative studies' below.)

In contrast, 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.

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 "Clinical use of 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.

A trial in which 94 children with molluscum contagiosum were randomly assigned to a single treatment of cantharidin without occlusion, cantharidin with occlusion, placebo without occlusion, or placebo with occlusion found a nonstatistically significant trend towards better outcomes with cantharidin [39]. Total clearance of molluscum lesions at week 6 occurred in 10 of 24 children (42 percent) in the cantharidin with occlusion group, 7 of 23 children (30 percent) in the cantharidin without occlusion group, 2 of 25 children (8 percent) in the placebo with occlusion group, and 3 of 22 children (14 percent) in the placebo without occlusion group. A post-hoc analysis that compared the combined cantharidin groups with the combined placebo groups found the response to cantharidin superior (36 versus 11 percent of patients achieved complete clearance, respectively).

In a retrospective study of 300 children treated with cantharidin (without occlusion) for molluscum, 90 percent of children had lesion clearance, and an additional 8 percent demonstrated improvement without complete clearance [40]. 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 [19]. 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 [40]. In general, treatment with cantharidin should be avoided on the face, genital, or perianal areas.

Common adverse effects include transient burning, pain, erythema, and pruritus [40]. Postinflammatory dyspigmentation may occur, but typically resolves over several months. While uncommon, scarring can occur as a consequence of cantharidin treatment [41].

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 [42]. 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 [43-45], 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 [46]. 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 [47]. 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 [34]. 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 [48]. Flu-like symptoms may also occur.

Potassium hydroxide — Potassium hydroxide (KOH), in concentrations of 5 or 10%, has been used for molluscum contagiosum [49-52]. Application frequency reported in the literature ranges from three times per week to twice daily.

In a trial in which 53 young children with molluscum contagiosum were randomly assigned to once-daily application of 10% KOH, 15% KOH, or placebo until complete clearance or a maximum of 60 days, more children in the 10% and 15% KOH groups achieved complete clearance than in the placebo group at day 60 (59, 64, and 19 percent, respectively) [53]. Common side effects included stinging and burning at the site of application.

In a subsequent trial by the same research group in which 91 children (ages 2 to 16) were randomly assigned to application of either 10% KOH or placebo once daily until clearance of lesions or up to a maximum of 30 days, 55 percent of children in the KOH group achieved at least a 75 percent reduction in the number of molluscum lesions within 33 days compared with only 16 percent in the placebo group [52]. Adverse events were more frequent in the KOH group, with local effects at the application site and infections as the most common adverse events. Approximately one-third of children in the KOH group discontinued treatment due to adverse events compared with none in the placebo group.

Lower concentrations of KOH might also be of benefit. In a series of 20 children treated twice daily with 5% KOH in an aqueous solution, all patients cleared within six weeks [51]. Treatment with KOH also has been compared with other therapies for molluscum in randomized trials [54-56]. (See 'Comparative studies' below.)

Stinging or burning sensations often accompany application of KOH [54], and may be reduced with the use of the 5% concentration [50]. 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) [35]. 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/lactic acid experienced side effects. Local irritation is common with the use of salicylic acid.

Use of salicylic acid in combination with sodium nitrite [57] or povidone iodine solution [58] 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 [59-62]. The mechanism of action is thought to involve the induction of local irritation that damages the viral protein-lipid membrane [63]. Data on the efficacy of these agents are limited to reports of clinical experiences [59-62].

Treatment with topical retinoids can begin every other day and can be increased to twice daily as tolerated [19]. Application is discontinued once local erythema develops [19]. Irritation and xerosis are expected side effects. Topical retinoids should not be used during pregnancy.

Other topical agents — Limited data suggest potential benefit of other agents, such as ingenol mebutate, berdazimer sodium, and silver nitrate paste, for molluscum contagiosum.

An unblinded trial in which 19 patients with molluscum contagiosum were randomly assigned to topical ingenol mebutate 0.015% gel applied once daily for three consecutive days per week until resolution or imiquimod 5% cream applied once daily for five days per week until resolution found complete clearance in 9 of 10 patients in the ingenol mebutate group compared with 3 of 9 patients in the imiquimod group at week 12 [64].

A phase 2, vehicle-controlled, randomized trial in which 256 patients with molluscum contagiosum were randomly assigned to different regimens of berdazimer sodium coadministered with hydrogel, an investigational nitric oxide releaser, or vehicle suggests benefit of this agent for molluscum contagiosum [65].

A paste containing 40% silver nitrate was reported to be effective in a series of 389 patients [66]. Topical phenol [67] and trichloroacetic acid [68,69] also have been used for molluscum contagiosum, but high risks for pain and scarring make these agents unfavorable options.

A nonprescription topical homeopathic agent that contains argentum nitricum, Echinacea angustifolia, Fucus vesiculosus, and Thuja occidentalis is marketed for the treatment of molluscum contagiosum. No published studies have evaluated the efficacy and safety of this product for molluscum contagiosum.

Other physical interventions — Pulsed dye lasers have shown efficacy in case reports and small uncontrolled studies [70-76]. 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 [70]. Use of topical anesthetics prior to pulsed dye laser treatment may help to reduce pain associated with laser therapy. Potassium titanyl phosphate (KTP) lasers [77], carbon dioxide lasers [78,79], 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 [67], removal with sterilized tweezers [80], needle penetration in combination with topical tretinoin [81], intralesional injection with Candida antigen [82], topical 20 to 35% trichloroacetic acid [83], and hyperthermia [84]. 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 [85,86]. 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 [86]. However, in a separate series of 14 children treated with cimetidine 40 mg/kg/day, only four children cleared within three months, and seven children showed no improvement [85]. 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.