Introduction
Warts and molluscum contagiosum (MC) are common viral skin infections that affect all age ranges, especially immunocompromised individuals and those who have close contact with others - such as physical intimacy or certain sports.1,2 While estimates of their prevalence range from 5.1% to 11.5%, the greatest incidence of warts and molluscum are observed in children between the ages of 1 to 14 years old.3,4 Transmission can occur through direct skin-to-skin contact or indirectly through fomites or the use of personal care items.5 Major types of cutaneous warts include common warts, flat warts, and plantar warts.6 Common warts present as irregularly surfaced, domed lesions with thrombosed capillaries upon paring of overlying hyperkeratotic debris, whereas flat warts are smooth, flat-topped variants often occurring on the face and extremities (Figures 1-2).6 Plantar warts resemble calluses on the plantar surface of the foot with a punctate pattern of multiple pinpoint blood vessels after paring (Figure 3).6 In contrast, MC lesions appear as firm, dome-shaped pink or skin-colored papules with a central umbilication **(Figure 4**).2 Their presentation is often in clusters or in a linear distribution.7 MC may be more diffuse and symptomatic in areas affected by atopic dermatitis (Figure 5). In addition to distinct clinical appearances, the two conditions also hold different viral etiologies. Warts are caused by the human papillomavirus (HPV),8 whereas MC is caused by the molluscum contagiosum virus, a poxvirus.1 Commonly utilized therapies for warts and MC include cryotherapy, curettage, imiquimod, and salicylic acid.9,10 However, given the lack of evidence-based treatment guidelines for warts and MC, the fact that they are sometimes refractory to conventional therapy, along with the benign nature of these conditions, patients and clinicians may be interested in trying complementary and alternative therapies. This review summarizes the clinical evidence surrounding the use of integrative therapies for warts and MC (Tables 1-3).
Integrative Therapies
Cantharidin
Cantharidin, a natural toxin produced by the blistering beetle, can treat warts and molluscum by inhibiting protein phosphatase and inducing vesiculation through acantholysis.11,12 While often compounded specifically for this purpose, two commercial formulations of cantharidin currently exist. Canthacur (0.7% cantharidin) is indicated for common warts, periungual warts, and molluscum contagiosum. The second formulation Canthacur PS (1% cantharidin, 30% salicylic acid, 2% podophyllotoxin) is indicated for plantar warts.11,13 In a 6-week randomized double-blind, placebo-controlled trial (RDBPCT), 36.2% of pediatric patients (ages 2 to 17 years old; n=94) diagnosed with MC achieved complete clearance when treated with 0.7% cantharidin solution vs. 10.6% with placebo (P= 0.0065).14 However, a systematic review of topical cantharidin treatment for warts and MC by Vakharia et al. suggests variable clearance rates ranging from 15.4 to 100% when treating MC with topical cantharidin. When topical cantharidin is used in combination with podophyllotoxin and salicylic acid, clearance rates improve to a range of 81-100%, with four studies noting 100% clearance.13 Pain (7-85.7%), blistering (10-100%), and hyper-/hypopigmentation (1.8-53.3%) are the most common adverse effects of cantharidin treatment.13 Notably, hyper-/hypopigmentation is common in patients with skin of color after both cantharidin and cryotherapy treatment, so this should be considered in patient care and counseling.10 Despite its efficacy and safety, cantharidin has yet to receive FDA approval, but this may change in the near future with VP-102.
VP-102 is a drug-device combination that contains a Good Manufacturing Practice (GMP)-controlled formulation of cantharidin (0.7% w/v) intended to treat common warts, external genital warts, and molluscum contagiosum. While it is currently under FDA evaluation, VP-102 has demonstrated potential in phase 2 and phase 3 clinical trials. In two identical phase 3 trials (CAMP-1 and CAMP-2; ≥ 2 years old, n=582), topical application of VP-102 or vehicle once every 21 days (for a maximum of 4 treatments) resulted in complete clearance of lesions by 46.3% (CAMP-1) and 54.0% (CAMP-2) of patients with VP-102 vs. 18% (CAMP-1) and 13% (CAMP-2) with placebo.15 The most common adverse events included moderate application site vesicles (43.5% and 20.0% in the VP-102 and placebo groups, respectively), pain (28.0% and 9.3%), pruritus (11.2% and 3.3%), erythema (23% and 18.7%), and scabbing (9.9% and 7.3%).
Essential oils
Some essential oils, such as those from Backhousia citriodora (lemon myrtle), Melaleuca alternifolia (tea tree), and Santalum album (sandalwood), have demonstrated anti-inflammatory, anti-microbial, and anti-proliferative properties that make them appropriate candidates for topical treatment of warts and MC with potentially minimal side effects. In a 3-week randomized controlled trial (RCT), children (mean age 4.6 ± 2.1 years; n=31) with MC were treated with once daily topical application of 10% solution of essential oil of Australian lemon myrtle leaf (B. citriodora) or vehicle control (olive oil).16 By day 21, complete clearance or reduction in lesions by at least 90% was achieved by 56.3% of patients treated with essential oil of B. citriodora vs. 0% in the control group (P < 0.05).16 No adverse events were reported from this study. Although the essential oil of Australian lemon myrtle appears moderately efficacious and safe in treating MC, further work is needed to identify the active ingredient(s) responsible for these clinical effects.
Essential oils of M. alternifolia (tea tree essential oil) have also demonstrated potential for treating MC. In a 4-week RCT, children (mean age 6.3 + 5.1 years; n=53) with MC were treated with twice daily topical application of a combination of essential oil of M. alternifolia and organically bound iodine (TTO-I), essential oil of M. alternifolia (TTO) only, or iodine only.17 By day 30, complete clearance or reduction in lesions by at least 90% was achieved by 84.2%, 16.7%, and 6.3% of patients treated with TTO-I, TTO, and iodine respectively (P<0.01).17 Although no adverse events were observed in this study, tea tree essential oil can cause allergic contact dermatitis in some cases.18
Sandalwood album oil (SAO), also known as East Indian sandalwood oil (EASO) derived from the S. album tree, may be beneficial in treating multiple skin conditions such as acne, psoriasis, atopic dermatitis, common warts, and MC.19 In a 12-week Phase 2 RDBPCT, adult patients (n=183) with common warts were treated with twice daily topical application of placebo, 10%, 20%, or 30% East Indian Sandalwood Oil (EISO). After 12 weeks, a reduction in warts by at least 75% was achieved by 9.5%, 11.1%, and 18.6% of patients treated with EISO 10%, 20%, 30%, respectively, vs. 4.7% of patients treated with placebo.19,20 No adverse events were observed in this study.
Oral propolis and Echinacea
Propolis is a resinous material from bees and plant buds/exudates that has demonstrated anti-bacterial, anti-fungal, anti-viral, and anti-inflammatory properties, thereby improving natural resistance to infection.21 When added to ointments, propolis has been suggested to promote healing of genital herpes lesions and reduce local symptoms.21 Another immunomodulator with antiviral properties, Echinacea (purple coneflower), also holds potential for treating warts.21 In a single-blind, randomized, 3-month trial, 135 patients with flat, plantar, or common warts were treated with 500 mg/day single oral dose of propolis, 600 mg/day oral Echinacea purpurea, or placebo.21 Complete clearance of common warts, flat warts, and plantar warts was achieved by 73%, 75%, and 17% of patients, respectively, when treated with propolis, compared to 20%, 36%, and 0% of patients treated with Echinacea purpurea.21 A significant difference was observed in the treatment of common and plantar warts by both propolis vs. Echinacea compared to placebo groups (p<0.05). More notably, by six months, none of the patients who achieved complete cure developed recurrent or new lesions.21 Though this particular trial reported no adverse events, other studies have reported significant side effects such as allergic reactions and skin or mucous membrane irritations from propolis when given at doses greater than 15 g/day.22 Caution should be taken with propolis when treating patients with asthma or eczema.22 At lower doses, however, the side effects of propolis were limited to isolated cases of allergy and contact dermatitis.23,24 In a separate RCT with adults and adolescents (n=172), the addition of nutraceutical oral supplementation (OS) with Echinacea to conventional standard therapy (CST) significantly reduced the number of warts at 6 months compared to CST alone.25 Complete remission was achieved in 86% vs. 54.5% of patients given CST or CST+OS treatments, respectively (P<0.001).25 No adverse events were observed in either trial nor with either medication. Furthermore, to the best of our knowledge, no English-language study has been published using propolis or Echinacea purpurea for MC.
Heat therapy
While cryotherapy is a standard of care in wart and molluscum treatment, heat therapy, or hyperthermia, has also been widely used, albeit to a lesser degree. In a RCT of 52 adult patients, one hyperthermic treatment exhibited a higher clearance rate of warts when compared to cryotherapy; however, the result was not statistically significant. Notably, there was a higher rate of post-treatment scarring with hyperthermia, with all incidents occurring in patients with skin phototypes IV or V and forearm or hand dorsum warts.26 In most cases, however, hyperthermia is advantageously non-destructive and can be delivered via a variety of treatment methods, including thermal water immersion, topical patches, and targeted devices.
The mechanism whereby elevated temperature may improve the clearance of warts or molluscum is still undetermined, although investigation has demonstrated multiple possibilities. Heat is thought to either inactivate or slow the spread of HPV to adjacent tissue, allowing the skin’s natural repair and shedding process to take place. Local hyperthermia has been shown in in vitro studies to lead to the upregulation of certain anti-viral proteins and cytokines, while downregulating those involved in cellular metabolism, protein translation, and keratinocyte differentiation.27,28
Thermal water immersion
Dating as far back as Greek mythology, the therapeutic benefits of thermal mineral water have been well-known around the world for centuries.29 Balneotherapy (BT) refers to treating disease by bathing in thermal mineral water, generally with patient immersion in baths or pools, and has a long history of use in inflammatory skin and rheumatologic diseases.30 When BT is combined with ultraviolet radiation phototherapy, augmenting the proposed anti-inflammatory effect, it is termed balneophototherapy (BPT). In the 1800s, BT first emerged as a treatment in Europe, soon followed by use in the United States.31 Its use decreased in the 20th century as more pharmacologic treatments became available. However, over recent decades, renewed interest has emerged in BT as an alternative or complementary treatment option with minimal side effects.
Skin inflammation may be decreased by the qualities of thermal waters,32 although there is a paucity of robust clinical evidence for BT and BPT. Treatment regimens lack standardized protocol, as factors including the chemical composition, hydrogeologic origin, duration of immersion, and temperature of thermal spring water used vary widely.32,33 Such heterogeneity in regimens complicates the ability to extrapolate and generalize the efficacy of BT and BPT in dermatology, and thus far, no randomized, placebo-controlled trials have been conducted.
Thermal spa bathing for 3 days was associated with complete clearance of recalcitrant warts in an organ transplant patient in one case.34 Warts are often recalcitrant in immunosuppressed patients, such as those with organ transplants, making BT/BPT an appealing option. However, when investigators attempted a study comparing thermal to hyperthermic tap water treatment between the right and left hand of five organ transplant patients with hand warts, no significant improvement in size or number of warts was noted after 12 sessions over one month. It was concluded that neither thermal spa nor hyperthermic tap water is effective in the treatment of resistant hand warts in organ transplant patients, while again noting that this cannot be generalized without testing thermal water from differing geographic sources.34
Targeted hyperthermia
In addition to aqueous immersion, hyperthermic wart therapy has been effectively applied in multiple cases as a targeted treatment. This allows for greater localization of heat to the wart compared to aqueous submersion of a larger anatomic area. However, notable variability exists in methods. Hyperthermic sources included microwave, radiofrequency, and thermal patches; temperatures range from 40°C to more than 50°C; and timing protocol has varied from seconds to hours of administration.35–38 Despite the inconsistencies in methodology, both adhesive epicutaneous patches and patented hyperthermic devices have demonstrated efficacy in multiple studies.
Topical heat patches
Exothermic patches deliver lasting and continuous heat over a period of time, and can be placed and managed by the patient. The self-administered design is very convenient and cost-effective for patients, necessitating fewer medical visits and expenses. Patients with recalcitrant warts experienced clearance of warts with such patches for at least 2 hours daily over 4-6 weeks at a safe temperature of 42-43ºC in five reported cases.36,39
Targeted devices
Targeted hyperthermic devices use radiofrequency-generated heat, with some designs making direct contact with the skin and others acting locally without direct contact. Subjects should experience a tolerable sensation of burning or some pain, with tolerance being generally higher on the feet.40 Older devices were often used with local lidocaine anesthesia,38 while in more recent studies, effective temperatures were titrated to subject tolerability without anesthesia. Multi-subject studies over 3 months using such devices reported resolution of warts in 53.6% to 86%, compared to 11.5% and 41% of controls in these studies, respectively.38,40,41 All patients remained clear of warts at later follow-up. Patients with load-bearing pain secondary to plantar warts also experienced benefit from localized hyperthermia, with 80% reporting decreased pain by 3 months.42
Regular local hyperthermia for 30 minutes at 44°C delivered with a controllable infrared device has also been used successfully for the treatment of disfiguring facial warts and extensive flat warts. Two cases of facial common warts successfully resolved in 10 and 12 weeks after treatment once a day for three consecutive days, and a repeat session two consecutive days a week later.43 In a case report of multiple warts present for over one year, lesions completely cleared over 2 months of treatment, with initial regression evident within the first week of treatment. The patient had no recurrence at 15 months of follow-up.44 Molluscum also has been demonstrated to respond to targeted hyperthermia although no data were found regarding other types of heat therapy for molluscum. Infrared device treatment at 44ºC for 30 minutes once a week led to total clearance of MC lesions in 57% of 21 patients ranging from ages 3 - 28 years old by 12 weeks, with no recurrence at 3 month follow-up.45
Oral and topical zinc
Zinc, a micronutrient required for normal cell functioning, is commonly used as a treatment for a variety of medical illnesses due to its immune-modulating effects and lack of serious complications. As a wart treatment, zinc has shown positive results in several clinical trials, although its efficacy has not been well-established.
A treatment regimen commonly used in published studies for oral zinc is 10 mg/kg (maximum dosage 600 mg) for 1-2 months. In patients with or without signs or symptoms of zinc deficiency, this regimen in three separate studies demonstrated improved wart regression to be associated with a rise in serum zinc levels.46–48 Patients in studies with long-term follow-up were observed to remain wart-free at 6-month follow-up in multiple studies.47,49 The most notable side effect was nausea, with between 16-100% of zinc-treated patients reporting nausea,48–50 occasionally significant enough to cause patient drop-out. Oral zinc may be a promising wart treatment, particularly for stubborn warts in children due to its painless and self-administered nature. However, nausea may limit its practice use. For this reason, oral zinc administration can be divided into three separate doses throughout the day with meals to ameliorate nausea.50
Zinc has also been used topically for warts, circumventing the side effect of nausea. In a randomized, double-blind controlled trial of 44 patients, 50% of patients treated with topical zinc oxide 20% ointment experienced complete cure of warts within three months, compared to 42% of controls, without any noteworthy side effects.51
Zinc, both oral or topical, is a cost-effective and relatively safe treatment, yet additional robust research is necessary to further evaluate its use in wart therapy. A 2021 systematic review reported that zinc therapy was found to be effective in 13 of 16 evaluated studies; six of these investigated isolated oral zinc supplementation, two explored oral zinc as an adjuvant therapy, five looked at intralesional zinc sulfate, and three examined topical zinc treatment.52 Overall, zinc holds its appeal as a wart treatment. Importantly, however, long-term ingestion of high-dose zinc may lead to copper deficiency and copper co-administrated should be considered in long-term use.53 To the best of our knowledge, no English-language study has been published using zinc for MC.
Hypnosis
Using hypnosis as a treatment method for warts dates back to the 1940’s.54,55 Over the years, multiple case reports and series have been published supporting a potential role for psychotherapy and hypnosis in the treatment of viral warts, particularly in children.56,57 In one case series, nine children under the age of 13 with warts on the hands, feet, and/or face were treated with simulated x-ray sessions.57 Patients were placed in front of an x-ray tube and the cooling unit was turned on but no voltage was set and thus no x-rays were produced. Parents were informed of the harmless nature of the treatment. Experimenters suggested to the patients that the x-rays would work on their warts and that they may feel a warmness in and around the wart later. Each “radiation” lasted 1 minute and therapy was repeated every 1-3 weeks. Five of the patients completely cleared their warts and three of them partially cleared them after an average of three treatment sessions. This is an example of a direct suggestion in hypnosis, in which a patient is told that they will feel a certain way. It has been suggested that children will almost always respond to direct suggestion in hypnosis, whereas adults will not.58
Hypnoanalysis, in which hypnosis is incorporated into psychoanalysis and psychotherapy, may work better for teens and adults.56,58 One case report found that five treatment sessions of psychotherapy with hypnosis spanning over seven weeks completely cleared a wart on the hand of a 16-year-old girl.56 The therapy focused on guided imagery and suggestions for optimizing the patient’s immune system. Another case series of 41 adults with warts found that 33 participants (80%) were cured with hypnoanalysis.58 Considering that warts may spontaneously resolve, it can be difficult to prove the true efficacy of hypnosis. However, since it is safe and noninvasive, hypnosis could be considered as an additional therapy for warts, particularly in children who may be more susceptible to suggestion. To the best of our knowledge, no English-language study has been published using hypnosis in the treatment of MC.
Garlic
Garlic has been used to treat warts in traditional Chinese medicine59 and has demonstrated in vitro antiviral properties.60,61 In a case series of five children, garlic was demonstrated to be an effective treatment method for palmar warts.62 Parents were instructed to rub the cut surface of a raw garlic clove onto their child’s wart, then cover with a bandage or waterproof tape overnight. All five children experienced clearing of their wart with improvement seen at an average of 3.2 weeks and complete clearance seen at an average of 9 weeks. One child reported itching, but the therapy was otherwise well-tolerated. In a larger study of both children and adults, 28 patients with 2–96 warts, nine patients with 1–2 corns, and a control group of five patients with 7–35 warts were treated with twice-daily aqueous garlic extract, lipid garlic extract, or a control solution.63 Authors found the lipid garlic extract to be more effective than the aqueous garlic extract, with near-complete clearance being achieved in all patients after 1-2 weeks of treatment with the lipid garlic extract versus only partial clearance after a treatment period of over 2 months in those applying aqueous garlic extract. No participant in the control group demonstrated any signs of clearance.
Patients using garlic therapy for warts should be counseled to avoid placing garlic on the healthy surrounding skin because garlic can cause a blistering contact dermatitis and chemical burns.64,65 To prevent such reactions, patients can coat the area around the warts with zinc oxide paste to protect the surrounding skin.63 If counseled on correct application, garlic offers a safe and cost-effective alternative therapy for the treatment of warts. To the best of our knowledge, garlic has not been explored in the literature as a treatment for MC.
Special considerations in treatment
Wart or molluscum treatment in certain populations such as children, pregnant patients, and those with diabetes mellitus can present additional challenges. Children tend to have significantly lower thresholds for pain and discomfort, making standard treatments such cryotherapy, laser, or surgical removal particularly challenging - especially for warts located in the genitalia or other sensitive areas. These same three treatment modalities are generally contraindicated for genital warts in pregnancy. In diabetes mellitus, defective immune responses lead to more extensive and persistent warts.
Multiple studies suggest that oral zinc may be an effective, safe, and painless wart treatment for children.46,47,49,50 Essential oils are also promising areas of investigation for painless molluscum treatment in children.12,13 Local hyperthermia has been successfully used to treat perianal and genital warts in both children and pregnant women in case reports, as a much more comfortable and less risky treatment option.66,67 In patients with diabetes, local hyperthermia also appears promising as a safe and effective treatment modality, with complete clearance within about 1-2 months in a case report.68
Conclusion
Despite the prevalence of warts and MC, no evidence-based treatment guidelines currently exist. As a result, some patients may turn to complementary and alternative therapies for relief. Promising data exists for many modalities of such integrative therapies. Cantharidin; essential oils such as those from Backhousia citriodora, Melaleuca alternifolia, and Santalum album; propolis; Echinacea; heat therapy; garlic; and zinc are examples of treatments with proposed anti-inflammatory, anti-proliferative, and/or immune-modulating effects that assist in clearing warts and MC. For children who tend to be more vulnerable to suggestion, hypnosis can be attempted as an alternative wart therapy. While additional research is required to understand the mechanism and true efficacy, the integrative therapies reviewed herein offer practical and relatively safe alternatives for the treatment of warts and MC.
Conflicts of Interest
Dr. Lio reports research grants/funding from AOBiome, Regeneron/Sanofi Genzyme, and AbbVie; is on the speaker’s bureau for Regeneron/Sanofi Genzyme, Pfizer, Incyte, Eli Lilly, LEO, Galderma, and L’Oreal; reports consulting/advisory boards for Almirall, ASLAN Pharmaceuticals, Bristol-Meyers, UCB, Dermavant, Regeneron/Sanofi Genzyme, Merck, Pfizer, LEO Pharmaceuticals, AbbVie, Eli Lilly, L’Oreal, Pierre-Fabre, Johnson & Johnson, Menlo Therapeutics, IntraDerm, Exeltis, AOBiome, Realm Therapeutics, Galderma, and Verrica.
The other authors report no conflict of interest.
Funding Sources
No funding sources were secured for this study.