Different Therapies to Treat Cutaneous Warts
Warts are benign skin lesions that occur in the mucosa and skin, and are caused by the human papillomavirus (HPV). Clinical manifestations of a common wart appear as a 1 mm to several centimeters papular lesion that can be rough, flat, or smooth in nature, and range from skin-colored to brown, or grayish-black. It is commonly seen in Caucasians, immunosuppressed individuals, and school-aged children. HPV viral replication occurs in the upper level of the epithelium and can be found in the basal layer. The warts appear commonly on the hands, feet, face, and genitalia. Different types of warts caused by HPV infection include common warts, genital warts, flat warts, and deep palmoplantar warts (Myrmecia). There are over 100 different types of HPV, and those associated with malignancies include HPV types 6, 1, 16, 18, 31, and 35. Individuals infected with genital warts and immunocompromised patients are more likely to develop malignancies. Likewise, HPV types 5, 8, 20, and 47 are associated with cancer that may lead to epidermodysplasia verruciformis, which is characterized by reddish-brown scaly patches or formation of wart-like lesions on the face, neck, hands, arms, legs, feet, and trunk. Warts are a communicable skin infection transferred by direct or indirect contact with the affected area. Damage to the epithelial barrier, for instance, a cut or scrape of the skin, increases the opportunity for HPV infection and wart development. Most warts resolve independently of treatment, and do not cause scarring if it disappears on its own. However, several surgical procedures and pharmacologic treatments are available.
Different wart-removing procedures include cryosurgery, electrosurgery and curettage, and laser treatment. Cryosurgery is a common treatment that involves freezing the wart via application of liquid nitrogen with a cotton swab against the affected area or sprayed with a nozzle. The extremely cold temperature destroys the surface of the skin, and there are multiple sessions involved. Electrosurgery and curettage involves burning the warts followed by curettage, which is scraping off the wart with a sharp device. Laser surgery involves heating and destroying the wart with a laser beam, such as pulsed dye laser treatment. Pulsed dye laser treatment involves the conversion of a concentrated beam of yellow light into heat, which targets the blood vessels that supply blood to the wart, thereby destroying the affected area and stopping cellular epithelial multiplication.
Pharmacological treatment of warts include salicylic acid, bleomycin injections, cantharidin, and systemic treatment with cimetidine. Salicylic acid is considered first-line, over-the-counter therapy that destroys the HPV-infected epidermis through induction of an immune response from mild irritation of the salicylic acid. It is available over-the-counter as 17% salicylic acid combined in a flexible collodion or as a 40% patch. Another treatment option is bleomycin injection, which is reserved for refractory warts. Bleomycin works by inhibiting DNA and protein synthesis of squamous cells and reticuloendothelial tissue. It causes acute tissue necrosis, stimulates the immune response, and destroys the wart. Expected adverse effects include pain and burning at the injection site and swelling. Moreover, cantharidin treatment is another option which is derived from the blister beetle, and is a vesicant. The liquid is applied to the wart and let dry with tape. Blister formation is expected, and the lesion may fall off or the blistered lesion is removed at the base. Cantharidin works by causing death of epidermal cells, and acantholysis, which is the loss of intercellular connections between epidermal cells. Systemic cimetidine is also another pharmacological treatment believed to work by inhibiting suppressor T-cell function and increasing lymphocyte proliferation, which leads to cell-mediated immune responses to destroy the wart. Cimetidine for wart treatment is given 20 to 40 mg/kg.
In conclusion, it is common for HPV-induced warts to resolve independently of therapy. However, invasive procedures and pharmacologic treatment are available for those who want immediate removal or for refractory or recurring warts.
Aboud, Ahmad M, and Pramad K Nigam. “National Center for Biotechnology Information.” Wart, 16 Apr. 2023, www.ncbi.nlm.nih.gov/books/NBK431047/.
Lipke, Michelle M. “An Armamentarium of Wart Treatments.” Clinical Medicine & Research, Dec. 2006, www.ncbi.nlm.nih.gov/pmc/articles/PMC1764803/#:~:text=Salicylic%20acid%20is%20a%20first,caused%20by%20the%20salicylic%20acid.
“National Center for Biotechnology Information.” What Are the Treatment Options for Warts?, 7 Nov. 2019, www.ncbi.nlm.nih.gov/books/NBK279585/.
“Warts: Diagnosis and Treatment.” American Academy of Dermatology, www.aad.org/public/diseases/a-z/warts-treatment. Accessed 5 June 2023.
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Another treatment is cantharidin 0.7%, also known as "beetle juice". It is a clinician-administered blistering agent commonly used for molluscum contagiosum. It can be used for warts because it is a painless application and it can easily treat multiple warts. Cantharidin is applied to individual warts and then covered with tape. The way it works is by blistering within 2 to 24 hours to remove the wart. The tape should then be removed and the medication should be washed off with soap and water. The major issue with this medication is the blistering. It can be uncomfortable and some patients may experience local swelling and significant pain. One of the major treatment concern is at the site called a doughnut wart. Cantharidin can be used every 3 weeks. If there is no response within 4 treatments, a different treatment option should be used. Studies for cantharidin are limited and it is not commercially available in the United States. It is used as a compounded product in Canada is commonly sent to the United States.
Topical salicylic acid is considered first line treatment for warts. It works by exfoliating the affected epidermis and stimulating a local immune reaction. A few advantages for the use of salicylic acid include self-administration, it is painless treatment, and there is a small risk of serious side effects. Salicylic acid products are usually made in concentrations between 17% and 50%, with the higher concentrations utilized for thicker skin areas. Salicylic acid is applied directly to the wart. The treated area should be dry prior to application, and the treatment should be repeated daily. Tape may be used to keep the salicylic acid on the proper location but it should be replaced every 48 hours. Treatment should not go on longer than 12 weeks without assessment by a physician. Soaking and paring of the wart should be repeated periodically to minimize build-up of hyperkeratotic debris. Salicylic acid is usually combined with other therapies, most frequently cryotherapy. The most common side effect is skin irritation and patients with peripheral neuropathy should avoid use. A 2012 meta-analysis of randomized controlled trials saw that salicylic acid was superior to placebo for the removal of warts (relative risk [RR] 1.56, 95% CI 1.20-2.03). Overall, the reports percentage of wart clearance when treating with salicylic acid therapy ranged from 0% to over 80%.
Pulsed dye lasers are another treatment option for warts. The laser used targets hemoglobin, resulting in the destruction of wart vasculature. Warts should be pared before the use of pulsed dye laser treatment. This therapy usually requires a series of treatments. Salicylic acid therapy shortly prior to laser therapy may reduce the number of treatments needed. Some side effects associated with this therapy include pain, blistering, dyspigmentation, and scarring. One of the largest studies on pulsed dye laser therapy was a retrospective study of 227 patients treated for recalcitrant common or plantar warts. The study found favorable results. In a mean of six treatments with high laser, 86% of the 209 patients achieved complete or almost complete resolution of their warts. Treatment intervals of every 3 to 4 weeks were associated with higher success rates as compared to longer therapy intervals.
Human papillomaviruses (HPVs) can infect the epithelial tissues of skin with the most common clinical manifestations of HPV infection presenting as a wart (verrucae). One treatment of cutaneous warts that I found interesting was cimetidine. Cimetidine has been shown to be effective in the treatment of therapy resistant or multiple viral warts. Cimetidine is a H2 receptor antagonist that is used based on the theory that H2 receptors are present on T-suppressor cells. By blocking these receptors, it is believed that it may result in an increase in cell-mediated immunity. Studies suggest that cimetidine therapy should be dosed at 30 to 50 mg/kg per day in four divided doses for up to three months. Although randomized trials have not found superiority over placebo. One study investigated 55 patients with multiple viral warts treated only with oral cimetidine for up to 4 months. The patients were divided into 2 groups. The first group, A received oral cimetidine dosed at <20 mg/kg/day. Group B patients received cimetidine dosed at 30 to 40 mg/kg/day. The study also measured mRNA levels of the cytokines interleukin-2 (IL-2), IL-18, and interferon (IFN)-gamma before and during treatment. As a result, 34.5% (19/55) of the patients had a dramatic clinical improvement or complete remission (CR) of their viral warts and 23.6% (13/55) of the patients had partial responses (PR) within 4 months of cimetidine therapy. IL-2 and IFN-gamma mRNA levels were significantly increased and IL-18 mRNA levels were decreased in tissues of effectively treated viral warts. The result showed that the higher dose of cimetidine were more effective in treating multiple viral warts compared to lower doses. They also found that cimetidine was able to activate Th1 cells to produce IL-2 and IFN-c and that the expression correlated with wart remission. These results suggest that cimetidine is an effective treatment for viral warts.