Key points

Common pediatric skin disorders can often be difficult to manage and studies of new treatment modalities in children are often lagging. This therapeutic update highlights some of the new literature on common infectious pediatric skin conditions (molluscum contagiosum [MC], warts, bacterial skin infections, and impetiginized atopic dermatitis) as well as 2 skin diseases that are often resistant to standard therapies (severe alopecia areata and vitiligo).

Molluscum contagiosum

MC is a poxvirus, which frequently affects children and is a common cause for visits to primary care doctors and dermatologists. Self-resolution of MC is the rule, but resolution can occasionally take many years. Parents often seek treatment for their children due to presence of concomitant dermatitis triggered or exacerbated by MC, risk of spread to other children, and social stigmata associated with visible lesions. Although there is still no Food and Drug Administration (FDA)-approved treatment for MC, different treatment modalities have been used by practitioners to speed clearance of the infection. In a survey of pediatric dermatologists performed by Coloe and Morrell, the most common treatment modality used was topical Cantharadin. Other treatments in descending order of frequency included topical imiquimod, active nonintervention, curettage, cryotherapy, retinoids (oral and topical), cimetidine, salicylic acid, duct tape, Candida antigen, potassium hydroxide, and cidofovir. Few published data are available on efficacy of these treatments though. Ideally, treatment of molluscum is painless yet effective with few side effects, given the young age group it commonly affects.

Immunotherapy has become a more popular treatment choice of pediatric dermatologists, given signs of good efficacy with fewer side effects than destructive methods in the recent literature. One common form of immunotherapy is intralesional Candida antigen injection. For MC, the technique involves injection of no more than 0.3 mL of Candida antigen into 1 to 3 molluscum intralesionally at each visit at 4-week intervals until clearance of infection is achieved ( Fig. 1 ). In a recent retrospective study by Enns and Evans, 29 children with MC were treated with Candida antigen. Total number of treatments ranged from 1 to 6. Complete clearance was seen in 16 (55.2%) patients after an average of 2.5 total treatments. Partial clearance was seen in 11 (37.9%) after an average of 3.3 treatments, for a total treatment response rate of 93%. Only 2 patients did not respond and the average number of treatments was only 1.5 in these 2 patients, which the investigators hypothesize as a possible reason for lack of response. Pain was the only reported side effect in 4 patients in this study. In a similar retrospective study by Maronn and colleagues, 47 patients with MC were treated with intralesional Candida antigen. Only 25 of these patients had follow-up, of whom 14 (56%) had complete clearance after an average of 3 treatments, 7 (28%) had partial clearance after an average of 4 treatments, and 4 (16%) had no improvement after an average of 3.33 treatments. No serious side effects were reported with use of the Candida antigen but most patients reported discomfort at the time of injection. Based on these 2 recent studies and anecdotal reports of success, intralesional Candida antigen injection offers a promising treatment of MC with few side effects. In the authors’ opinion, Candida injection is a good option in patients who have many molluscum or concomitant dermatitis where destructive modalities may be irritating to the skin.

Intralesional injection technique for Candida antigen into molluscum contagiosum.

( Courtesy of University of Colorado Dermatology Department.)

Imiquimod 5% cream is another attractive treatment of cutaneous viral infections, given the ability for home application and lack of pain with application. Imiquimod exhibits antiviral and antitumor effects through activation of the innate immunity and up-regulation of cytokines, such as interferon-α. In a small pharmacokinetic and safety study of imiquimod 5% cream in children with MC, when applied 3 times weekly for 4 weeks, low systemic drug levels were found and there were no serious adverse events, although application site reactions were reported in more than half of the participants. Although clinical efficacy was not an endpoint of this study, no subjects had complete clearance of their MC in the short 4-week treatment time. In other recent studies, longer-duration imiquimod use has shown promise as an effective treatment of MC. In a prospective study by Al-Mutairi and colleagues, the investigators compared the efficacy, safety, and acceptability of imiquimod 5% cream versus cryotherapy for MC. Imiquimod cream was applied 5 times weekly for up to 16 weeks in group A (37 patients) and cryotherapy was performed with liquid nitrogen for 2 10-second to 20-second cycles in group B (37 patients) at initial visit and 1 week later if needed. The investigators found more rapid clearance in the cryotherapy group with 100% clearance by 6 weeks, whereas the imiquimod group only had complete clearance in 22 (approximately 60%) by 6 weeks. By 12 weeks, however, no statistical difference was seen in MC clearance rates between the 2 groups, with approximately 92% complete clearance in the imiquimod group and 100% clearance in the cryotherapy group. At the 6-month follow-up, the cosmetic outcome was superior in the imiquimod-treated group, with only 2 patients having residual hypopigmentation versus 15 patients in the cryotherapy group with residual pigmentary alterations and 8 patients with scarring or atrophy, which was statistically significant. Relapse was seen in 3 patients in the cryotherapy group at 6 months and no relapse was seen in the imiquimod group, possibly due to the broader immune up-regulation seen with imiquimod versus destructive modalities. Imiquimod seems to have promise as an effective treatment of MC, especially for multiple small papules and in sensitive areas, such as the face and anogenital region; however, families should be educated on the potential high cost of the medication, long duration of treatment often needed, and the likelihood of erythema or other application site reaction with use.

No discussion of MC treatment is complete without an update on destructive modalities, which are still the most commonly used treatments by practitioners, including cantharadin and curettage as the most commonly used methods. Both cantharadin and curettage are effective, but past studies have shown that multiple treatments are necessary with frequent relapse and side effects, including severe blistering reactions as well as pain. The limitation of these 2 modalities is their relative contraindication for facial molluscum. Other treatment options for facial molluscum include topical 20% to 35% trichloroacetic acid. This technique was reported by Bard and colleagues, using the pointed edge of a broken cotton tip applicator with a small amount of trichloroacetic acid to the molluscum until a white frost appeared. They report minimal irritation and good efficacy with this technique. Another destructive modality with promise for practitioners with access to a pulsed dye laser (PDL) has been reported by Chatproedprai and colleagues. In this prospective study of 20 children, 81% of patients treated with the 585-nm PDL with 1 or 2 total treatments had clearance of their molluscum versus 23% spontaneous clearance of molluscum in control patients.

Molluscum contagiosum

MC is a poxvirus, which frequently affects children and is a common cause for visits to primary care doctors and dermatologists. Self-resolution of MC is the rule, but resolution can occasionally take many years. Parents often seek treatment for their children due to presence of concomitant dermatitis triggered or exacerbated by MC, risk of spread to other children, and social stigmata associated with visible lesions. Although there is still no Food and Drug Administration (FDA)-approved treatment for MC, different treatment modalities have been used by practitioners to speed clearance of the infection. In a survey of pediatric dermatologists performed by Coloe and Morrell, the most common treatment modality used was topical Cantharadin. Other treatments in descending order of frequency included topical imiquimod, active nonintervention, curettage, cryotherapy, retinoids (oral and topical), cimetidine, salicylic acid, duct tape, Candida antigen, potassium hydroxide, and cidofovir. Few published data are available on efficacy of these treatments though. Ideally, treatment of molluscum is painless yet effective with few side effects, given the young age group it commonly affects.

Immunotherapy has become a more popular treatment choice of pediatric dermatologists, given signs of good efficacy with fewer side effects than destructive methods in the recent literature. One common form of immunotherapy is intralesional Candida antigen injection. For MC, the technique involves injection of no more than 0.3 mL of Candida antigen into 1 to 3 molluscum intralesionally at each visit at 4-week intervals until clearance of infection is achieved ( Fig. 1 ). In a recent retrospective study by Enns and Evans, 29 children with MC were treated with Candida antigen. Total number of treatments ranged from 1 to 6. Complete clearance was seen in 16 (55.2%) patients after an average of 2.5 total treatments. Partial clearance was seen in 11 (37.9%) after an average of 3.3 treatments, for a total treatment response rate of 93%. Only 2 patients did not respond and the average number of treatments was only 1.5 in these 2 patients, which the investigators hypothesize as a possible reason for lack of response. Pain was the only reported side effect in 4 patients in this study. In a similar retrospective study by Maronn and colleagues, 47 patients with MC were treated with intralesional Candida antigen. Only 25 of these patients had follow-up, of whom 14 (56%) had complete clearance after an average of 3 treatments, 7 (28%) had partial clearance after an average of 4 treatments, and 4 (16%) had no improvement after an average of 3.33 treatments. No serious side effects were reported with use of the Candida antigen but most patients reported discomfort at the time of injection. Based on these 2 recent studies and anecdotal reports of success, intralesional Candida antigen injection offers a promising treatment of MC with few side effects. In the authors’ opinion, Candida injection is a good option in patients who have many molluscum or concomitant dermatitis where destructive modalities may be irritating to the skin.

Intralesional injection technique for Candida antigen into molluscum contagiosum.

( Courtesy of University of Colorado Dermatology Department.)

Imiquimod 5% cream is another attractive treatment of cutaneous viral infections, given the ability for home application and lack of pain with application. Imiquimod exhibits antiviral and antitumor effects through activation of the innate immunity and up-regulation of cytokines, such as interferon-α. In a small pharmacokinetic and safety study of imiquimod 5% cream in children with MC, when applied 3 times weekly for 4 weeks, low systemic drug levels were found and there were no serious adverse events, although application site reactions were reported in more than half of the participants. Although clinical efficacy was not an endpoint of this study, no subjects had complete clearance of their MC in the short 4-week treatment time. In other recent studies, longer-duration imiquimod use has shown promise as an effective treatment of MC. In a prospective study by Al-Mutairi and colleagues, the investigators compared the efficacy, safety, and acceptability of imiquimod 5% cream versus cryotherapy for MC. Imiquimod cream was applied 5 times weekly for up to 16 weeks in group A (37 patients) and cryotherapy was performed with liquid nitrogen for 2 10-second to 20-second cycles in group B (37 patients) at initial visit and 1 week later if needed. The investigators found more rapid clearance in the cryotherapy group with 100% clearance by 6 weeks, whereas the imiquimod group only had complete clearance in 22 (approximately 60%) by 6 weeks. By 12 weeks, however, no statistical difference was seen in MC clearance rates between the 2 groups, with approximately 92% complete clearance in the imiquimod group and 100% clearance in the cryotherapy group. At the 6-month follow-up, the cosmetic outcome was superior in the imiquimod-treated group, with only 2 patients having residual hypopigmentation versus 15 patients in the cryotherapy group with residual pigmentary alterations and 8 patients with scarring or atrophy, which was statistically significant. Relapse was seen in 3 patients in the cryotherapy group at 6 months and no relapse was seen in the imiquimod group, possibly due to the broader immune up-regulation seen with imiquimod versus destructive modalities. Imiquimod seems to have promise as an effective treatment of MC, especially for multiple small papules and in sensitive areas, such as the face and anogenital region; however, families should be educated on the potential high cost of the medication, long duration of treatment often needed, and the likelihood of erythema or other application site reaction with use.

No discussion of MC treatment is complete without an update on destructive modalities, which are still the most commonly used treatments by practitioners, including cantharadin and curettage as the most commonly used methods. Both cantharadin and curettage are effective, but past studies have shown that multiple treatments are necessary with frequent relapse and side effects, including severe blistering reactions as well as pain. The limitation of these 2 modalities is their relative contraindication for facial molluscum. Other treatment options for facial molluscum include topical 20% to 35% trichloroacetic acid. This technique was reported by Bard and colleagues, using the pointed edge of a broken cotton tip applicator with a small amount of trichloroacetic acid to the molluscum until a white frost appeared. They report minimal irritation and good efficacy with this technique. Another destructive modality with promise for practitioners with access to a pulsed dye laser (PDL) has been reported by Chatproedprai and colleagues. In this prospective study of 20 children, 81% of patients treated with the 585-nm PDL with 1 or 2 total treatments had clearance of their molluscum versus 23% spontaneous clearance of molluscum in control patients.

Warts

Along the same lines as MC, warts (including common warts, flat warts, palmoplantar warts, and genital warts) occur frequently in children, affecting teenagers more commonly, and are a frequent cause of dermatology visits. Treatment options of warts are similar to those of MC, including topical salicylic acid, cryotherapy, cantharadin, duct tape, PDL, retinoids, podophyllin, and immunotherapies, such as cimetidine, zinc, squaric acid dibutylester (SADBE) and diphencyprone (DPC), Candida antigen, and imiquimod. More-aggressive treatments include intralesional bleomycin, intralesional or topical 5-fluorouracil (5-FU), and interferon. Imiquimod is the only medication with FDA approval for warts (genital warts only) in children 12 years or older.

Few new data are available on novel or established wart treatments. Intralesional Candida antigen was initially used for the treatment of warts before its recent reported use in MC. Candida antigen is an excellent treatment option when multiple warts are present. In a retrospective study, Maronn and colleagues treated 170 wart patients with Candida antigen injections. The technique involved 0.3 mL injected into 1 or 2 warts at monthly intervals. Unfortunately, they had a low follow-up rate in this study, but complete clearance was seen in 48/55 (87%) of patients with follow-up after an average of 3.5 treatments. Only 4/55 (7%) had no improvement after an average of 3.75 treatments. Along the same immunotherapy line, both SADBE and DPC have been reported recently as effective in treatment-resistant warts. Both of these agents require sensitization followed by application to warts once weekly up to nightly. In a recent study by Choi and colleagues, they found that DPC and cryotherapy had equal initial complete clearance rates (62.5% vs 50.8%, respectively); however, at 12 months’ follow-up, of those with complete clearance, the DPC group had 93% sustained clearance versus 76% in the cryotherapy group. The investigators hypothesized that DPC induced long-term immunity to human papilloma virus. A recent case report also demonstrated efficacy of SADBE in an immunosuppressed patient in multiple modality treatment-resistant warts.

Oral zinc supplementation has recently been reported as a promising new immune modulating treatment for warts. A randomized, placebo-controlled study by Yaghoobi and colleagues treated 32 children and young adults with zinc sulfate (10 mg/kg/d, maximum 600 mg daily) for up to 2 months’ duration and 23 patients received placebo. Complete clearance of all warts was seen in 25/32 (78%) patients receiving zinc and 3/23 (13%) placebo patients, with no recurrence of warts at 6-months’ follow-up. The investigators found that patients whose warts responded well to zinc treatment had dramatic increases in serum zinc levels, whereas nonresponders’ serum levels only increased a small amount. The investigators did not discuss any side effects associated with oral zinc treatment. In another small study by Stefani and colleagues, 9 patients were given high-dose zinc sulfate (10 mg/kg/d) and 9 patients were given oral cimetidine (35 mg/kg/d) for 3 months. Five of 9 patients in the zinc sulfate group had complete clearance versus no complete clearance of warts in the cimetidine group. In this study, 5 of 9 patients in the zinc treatment group reported nausea, causing 1 6-year-old patient to drop out of the study. The investigators recommend dividing the zinc into 3 daily doses with meals to attenuate nausea. In a larger study of zinc versus placebo for recalcitrant warts, 20 of 23 patients in the zinc group had complete clearance of warts versus 0 of 20 in the placebo group after 2 months of treatment. All of the patients in the zinc-treated group reported nausea. The study also had a 46% dropout rate, which may have skewed results. In the authors’ opinion, zinc seems potentially a great treatment option for recalcitrant warts in children because it is painless and can be administered at home. Good preliminary efficacy results have been shown; however, the nausea may limit actual long-term use.

Topical 5-FU is a chemotherapeutic agent frequently used for nonmelanoma skin cancers and warts in adults. In a study by Gladsjo and colleagues, 5-FU was studied with once-daily and twice-daily dosing in children with at least 2 common hand warts for 6 weeks under occlusion. Of the 39 total subjects (19 once-daily and 20 twice-daily dosing), there was no significant difference in improvement between the treatment protocols. Only 13% showed complete clearance of all warts at the end of the 6-week treatment period, although at least some improvement was seen in size or thickness of 88% of all treated warts. 5-FU levels were not measurable in 38 of the 39 subjects and no changes in complete blood count or liver function tests were observed in any subject. Although results from this study are not staggering in efficacy, the data are reassuring that the 5-FU may provide a well-tolerated, safe treatment of warts in children; however, over-the-counter salicylic acid treatments have more proved efficacy at a lower price point.

Laser treatment of warts is increasing, with reports of efficacy of the PDL predominantly in the past. Recently, a large series of 348 patients using the long-pulsed Nd:YAG laser in children and adults with warts showed an impressive overall complete clearance rate of 96%. Laser treatments were performed every 4 weeks for a maximum of 4 treatments. The investigators found that more than 72% of common warts cleared after 1 laser treatment, whereas periungual and deep palmoplantar warts were slower to respond (64% and 44% clearance after one laser treatment, respectively). Pain was the reported by most patients when just topical anesthesia was used; therefore, lidocaine injections were recommended for the pain accompanying the laser procedure, which may be prohibitory in some children. Otherwise, side effects reported were very low, including bullae formation, dyspigmentation, and nail dystrophy. For dermatologists with access to lasers, this promising treatment can be used.