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Treatment tips for molluscum contagiosum, warts.

EXPERT ANALYSIS AT PDA 2015

PARK CITY, UTAH -- In her practice as a pediatric dermatologist, Dr. Sheryll L. Vanderhooft sees her share of children who present with molluscum contagiosum and warts. At the annual meeting of the Pacific Dermatologic Association, she shared her approach to caring for patients who present with these two common conditions.

The root cause of molluscum contagiosum is a poxvirus infection that spreads by skin-to-skin contact. It takes an average of 6 months to 2 years for the host immune response to occur. "During that time parents panic and some need a lot of hand-holding," said Dr. Vanderhooft, professor of pediatric dermatology at the University of Utah School of Medicine, Salt Lake City. "They seek treatment primarily due to associated dermatitis triggered or exacerbated by the virus. There's also the risk of spreading the condition to other children and the stigma of visible lesions."

No Food and Drug Administration-approved therapies for molluscum contagiosum currently exist. "There are many options, but none of them are guaranteed to hasten resolution," she said. "This is a very important point to deliver to parents before you start trying to do a lot of therapy."

Common treatment options are cryotherapy and cantharadin destruction, curettage, treatment with topical imiquimod or retinoids, oral cimetidine, and injections of Candida antigen.

According to two retrospective studies of Candida antigen injection, complete clearance occurred in 56% of patients after an average of three treatments, while partial clearance occurred in 28%38% of patients after an average of four treatments (Pediatr Dermatol. 2008;25:189-92 and Pediatr Dermatol. 2011;28:254-8). The main side effect was local pain from the injections.

Antiviral and antitumor effects are seen with imiquimod cream through activation of the innate immunity and upregulation of cytokines, such as interferon-alpha, Dr. Vanderhooft said. Imiquimod iis FDA approved for genital and perianal warts in patients older than 12 years of age, as well as for actinic keratosis, superficial basal cell carcinoma, and antiviral-resistant herpes simplex virus in patients older than 12 years of age.

In a prospective study, researchers compared imiquimod cream given five times per week for up to 16 weeks with cryotherapy for the treatment of molluscum contagiosum in children (Pediatr Dermatol. 2010;27[4]:388-94). More than half of patients (60%) achieved clearance by week 6 and 92% achieved clearance by week 12. There were no relapses observed at 6 months.

"Liquid nitrogen cleared the lesions faster, but caused more postinflammatory dyspigmentation, and there were a few relapses in this group," Dr. Vanderhooft said.

The downside to imiquimod treatment is that it requires prolonged use, it's expensive, "and a lot of insurance companies will not pay for it because it's not FDA approved for young children," she said. "It can also cause irritant dermatitis, which is a difficult problem when you already have a kid who may be atopic and you're trying to treat molluscum." Also, according to the package insert for Aldara cream, imiquimod administered three times per week for 16 weeks was not shown to be superior to vehicle alone in two randomized, controlled trials that were completed in 2006 but never published. There were 323 children in one study, with complete clearance at 18 weeks in 24% of children treated with imiquimod, compared with 26% of children treated with vehicle alone.

There were 379 in the second study with complete clearance in 24% and 28% of children, respectively.

Children who were treated with imiquimod in these two studies were more likely to experience application site reactions, otitis media, and conjunctivitis. In addition, a pharmacokinetic study of 22 children with molluscum involving at least 10% of body surface area showed systemically detectable drug levels after single and multiple doses given 3 times a week for 4 weeks. The findings from these three studies led to changes in the FDA approved package insert in 2008. Section 1.4 of the "indications and usage" section of the package insert now reads: "Aldara cream has been evaluated in children ages 2-12 years with molluscum contagiosum and these studies failed to demonstrate efficacy." With that in mind, Dr. Vanderhooft's recommendation "is to either stop prescribing it in children or prescribe it once daily or twice daily as tolerated, not every other day."

While molluscum contagiosum is caused by a poxvirus, warts are growths on the skin caused by infection with human papillomavirus (HPV). On average, 75% of children will develop immunity to HPV within 3 years, "whether you do nothing, or whether you try to treat it," she said. "Parents seek treatment when the warts are large, spreading, or causing social stigma. There are many treatment options, but none are guaranteed to hasten resolution. This needs to be driven home to patients when you're counseling them." Treatments range from destruction with cryotherapy and pulsed-dye laser to salicylic acid and various topical or injectable agents. The only FDA-approved option is imiquimod cream, which is approved for genital and perianal warts only in patients 12 years of age and older.

In Dr. Vanderhooft's experience, Candida antigen injections benefit some patients. After injection of 0.3 mL of Candida antigen into one or two warts at monthly intervals, researchers in one study observed complete clearance in 87% of patients after an average of 3.5 treatments, while 7% had no improvements after an average of 3.75 treatments (Pediatr Dermatol. 2008;25:189-92).

In a randomized trial, researchers who evaluated oral zinc supplementation versus placebo for 2 months found complete clearance in 20 out of 23 patients in the treatment group (87%), compared with none of the 20 patients in the placebo group (Br J Dermatol;2002:146[3]:423-31). All patients in the zinc group reported nausea. "That's what has limited zinc therapy in my patient population," Dr. Vanderhooft said.

In a more recent study, researchers conducted a placebo-controlled study of zinc sulfate 10 mg /kg per day (up to 600 mg /day) for up to 2 months (J Am Acad Dermatol. 2009;60[4]:706-8). Complete clearance of all warts was achieved in 78% of patients in the treatment group, compared with 13% in the placebo group. No recurrence of warts was observed at the 6-month follow-up.

Topical 5-fluorouracil has also been evaluated for warts. One study of once or twice daily application of 5-FU under occlusion for 6 weeks led to improvement in 88% of patients, including 13% with complete clearance (Br J Dermatol. 2011;165[2]:233-46). No blood levels of the drug were detected. "It's thought to be safe and well-tolerated, but over-the-counter salicylic acid has better efficacy and is quite a bit cheaper," Dr. Vanderhooft said.

Another strategy for recalcitrant warts involves administration of squaric acid dibutyl ester (SADBE). In a recent retrospective chart review conducted over a 10.5-year period, researchers evaluated 72 children with recalcitrant warts who had failed therapy with multiple agents and were followed for a period of 6 months to 11 years (Pediatr Dermatol. 2015;32:85-90). The protocol involved sensitizing the children to 2% SADBE.

The treatment then started 2 weeks later, with 0.4% SADBE applied three times per week initially, with an extra day added per week as tolerated to reach daily use if possible. Of the 48 patients treated, 40 (83%) in whom treatment outcomes could be obtained reported complete resolution of their warts. Seventy percent of patients used a maximum concentration of 0.4% SADBE and 60% of patients reported no adverse effects.

The average time to reduction in size of warts was 2.6 months after sensitization, and treatment continued for a mean of 8 months.

Dr. Vanderhooft reported having no financial disclosures.

dbrunk@frontlinemedcom.com

Caption: Of 48 patients treated with 0.4% SADBE, 40 (83%) reported complete resolution of their warts.

DR. VANDERHOOFT

Caption: None of the treatments for molluscum are guaranteed to hasten resolution.

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Title Annotation:PEDIATRIC DERMATOLOGY
Author:Brunk, Doug
Publication:Dermatology News
Date:Oct 1, 2015
Words:1318
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