Viral Skin Infections
Among the most common manifestations of viral skin infections are warts caused by strains of human papilloma virus (HPV) (Cardoso 2011). Another common viral skin infection, molluscum contagiosum, is caused by a virus in the poxvirus family. Skin is also a target of herpes simplex viruses, which cause oral and genital herpes. Reactivation of the chickenpox virus ( Varicella zoster virus) causes shingles (Cevasco 2010). Additional information is available in the Herpes and Shingles protocol.
In general, viral skin infections are more common in immune-compromised individuals, who are also more likely to experience severe and recurrent outbreaks and complications (Cardoso 2011; Bader 2013; Sauerbrei 2016).
HPV-related warts affect an estimated 10% of the population. Fleshy papules (raised areas) are common. Other types of warts include plane (flat) warts, plantar warts (affecting the soles of the feet), and condyloma acuminatum (cauliflower-like growths, usually affecting the genital area) (Cevasco 2010; Kollipara 2015). Although the vast majority of warts are benign, some HPV strains have the potential to cause malignant growths (Cardoso 2011).
Molluscum contagiosum, which typically manifests as multiple wart-like lesions, affects nearly 5% of the population. Infection is frequent in children, people with compromised immune systems, and sexually active adults (Cevasco 2010). Molluscum cantagiosum resolves without treatment, but typically persists for 6 to 12 months and may last as long as five years (Butala 2013).
Conventional Treatment of Viral Skin Infections
Prevention is key in the battle against HPV-induced viral skin infections. The HPV vaccine can prevent genital warts: a large study conducted in Denmark reported that three injections provide complete protection (Thappa 2016; Blomberg 2015). The vaccine targets HPV subtypes associated with genital warts and cancers of the cervix and oropharynx (mid-throat) (Kim 2016).
Warts are most frequently treated with destructive (eg, cryosurgery), anti-proliferative, or antiviral agents applied topically or intralesionally (injected into the wart) (Cevasco 2010; Thappa 2016). Topical and intralesional treatments require multiple applications over a period of weeks. In general, side effects of these therapies include local irritation, burning, redness, and pain (Kollipara 2015; Thappa 2016). Topical imiquimod (Aldara), an immune-modulator that stimulates antiviral and antitumor immune activities, is approved for use in treating anogenital warts (Hanna 2016). The usefulness of imiquimod and other immunotherapies in the treatment of cutaneous warts is still being explored (Thappa 2016).
Cimetidine is an over-the-counter heartburn drug with interesting immune-modulating properties. Cimetidine has been shown to be an effective treatment for viral warts. One study showed that treatment with cimetidine alone for four months led to complete remission in 19 of 55 people with multiple viral warts. The drug produced partial remission in another 13 individuals. This study found that higher doses of cimetidine (30–40 mg/kg/day) were more effective than lower doses (less than 20 mg/kg/day). Although the precise mechanism by which cimetidine treats warts is not clear, the previously described study found that treatment with the drug increased levels of some immune-stimulating cytokines and activated a subset of T cells involved in antiviral defense (Mitsuishi 2003). Overall, data regarding the efficacy of cimetidine in treating viral warts are somewhat mixed, and larger, well-controlled studies are needed. Some studies and case reports to date have shown success in children with viral warts (Kharfi 2002; Chern 2010; Franco 2000), but evidence for efficacy in adults is less convincing (Rogers 1999).
Surgical removal of warts is sometimes preferred, but may require repeated surgery (NLM 2017b; Cevasco 2010).
Intralesional injections of microbial antigens and photodynamic therapy are new and promising treatments for genital and non-genital warts. These approaches are discussed in the Novel and Emerging Therapies section.
Integrative Treatment of Viral Skin Infections
In a controlled trial, 28 patients with at least two warts that were unresponsive to prior treatment were treated topically with either a water extract or a lipid extract of garlic (Allium sativum), applied twice daily. Five patients with warts served as the control group and were treated with the lipid solvent with no garlic. Complete resolution was seen within two week in all participants with warts treated with the lipid extract of garlic. Slower and less complete improvements were seen in those treated with the water extract, and no improvement was seen in the control group. Garlic use was associated with several side effects, including redness, burning, and blistering of the surrounding skin, but the side effects usually subsided in one to two weeks (Dehghani 2005). Another study used a similarly prepared lipid garlic extract on warts that had not responded to other treatments in 25 participants. Another 25 participants served as controls and were treated with saline. The duration of treatment was until the warts cleared or up to four weeks. Complete responses, defined as disappearance of the wart and return of normal-appearing skin, were achieved in 96% of subjects treated with the lipid garlic extract. No side effects were reported during lipid garlic extract treatment in this study (Kenawy 2014).
Low serum zinc levels were found in one study to correlate with persistent, progressive, and recurrent warts (Raza 2010). In a clinical study, a topical 10% zinc sulfate solution was more effective than placebo for treating plane and common warts (Sharquie 2007). Other clinical trials indicate oral zinc sulfate, at a daily dose of 10 mg/kg body weight, may also lead to successful resolution (Mun 2011; Al-Gurairi 2002). In one of these studies, 10 mg/kg zinc sulfate daily led to complete wart resolution in two months of treatment in half of participants that completed the study (Mun 2011). A study in children ages five to 11 showed that four weeks of treatment with a topical preparation containing zinc oxide and colloidal oatmeal extract led to partial or complete remission in all participants (Safa 2010).
Topical preparations made with vitamin D analogs have benefited patients with viral warts (Imagawa 2007; Moscarelli 2011). In addition, one study examined the effect of vitamin D3 injections into plantar warts. In 20 subjects with one or more plantar warts, 16 (80%) experienced complete resolution and one experienced partial resolution (Aktas 2016). One report described a case of an anogenital wart in an infant treated successfully with a topical vitamin D3 derivative (Rind 2010).
A number of studies have demonstrated positive outcomes using topical preparations with 10% and 15% green tea (Camellia sinensis) extract in patients with external genital and perianal warts (Gupta 2015; Scheinfeld 2013b). In two randomized controlled trials, green tea ointment, applied three times daily for up to 16 weeks, was more effective than placebo in clearing external anogenital warts (Hoy 2012). This evidence led the US Food and Drug Administration (FDA) to approve the use of a green tea catechin ointment called polyphenon E (Veregen) for treatment of HPV-related external anogenital warts (Stockfleth 2014).
In a clinical trial, 172 subjects with one or more warts were treated with standard therapy alone (salicylic acid plus lactic acid or liquid nitrogen cryotherapy) or standard treatment plus a four-month oral supplement regimen that included probiotics, methionine, echinacea, zinc, and other immune-stimulating nutrients. After six months, the group that received the supplements had fewer warts and a higher remission rate than the standard treatment group. Complete remission was achieved in 86% of subjects treated with the standard therapy plus oral supplements (Cassano 2011).
Emerging Therapy: Microbial Antigens
Microbial antigen therapy involves the injection of microbial antigens directly into warts (intralesional injections) to stimulate a strong local immune response. Extracts made from Mycobacterium w,Candida albicans, Bacillus Calmette-Guerin, and Trichophyton species, as well as tuberculin protein and the measles, mumps, and rubella vaccines have been used in early research against both genital and non-genital warts. Common side effects associated with this treatment include pain, redness, and swelling at the injection site, and systemic flu-like symptoms (Thappa 2016; Aldahan 2016). Some intralesional injection preparations are currently available, and are indicated in people with persistent, recurrent, or extensive warts, or in those with warts in hard-to-treat locations (Thappa 2016; Mulhem 2011).