Management of Warts

What are warts?

• Warts are benign growths caused by infection of keratinocytes by HPV, most often on the hands and feet.^1-3 The virus likely enters the skin through small lesions or cuts on the skin.¹
• Warts can sometimes be on the face and other areas and are more commonly seen in children.³
• Common warts, also called verruca vulgaris, are skin-colored (or occasionally darker) papules with a rough surface, and can have black dots (small, clogged blood vessels).^1,3
• Plantar warts, also called verruca plantaris, are found on the soles of feet and often look like very thick calluses.¹ They can be clustered, painful (feel like pebbles in your shoe), can have black dots (small, clogged blood vessels), and are typically harder to treat than common warts.³
• Flat (or plane) warts are smaller and smoother than other warts, can occur anywhere (often on the face in children or back of the hands), and tend to grow in large numbers (e.g., 200 to 100 at a time).^1,3
• Filiform warts look like thin fingers or projections that stick out, are often isolated on the face (e.g., around eyes or lips), and grow quickly.³

How can you prevent warts from spreading?

• Warts are contagious. The HPV virus can spread by direct contact or by touching contaminated objects 
   (e.g., a towel, fingers).
• Risk factors for warts include communal showers, occupational handling of meat, immunosuppression, etc.¹
• To try and help prevent the spread of warts:
  • Do not pick, scratch, or touch warts on self or others.^3,5
  • Wear flip-flops or other shoes in public spaces (pools, locker room showers, etc).^3,5
  • Wash your hands often, especially after touching the wart.³
  • Avoid shaving over a wart.³ If shaving, use an electric razor.⁵
  • Avoid sharing towels, washcloths, razors, nail clippers, etc.³

What are education points for patients asking about wart treatment?

• Warts don’t necessarily need to be treated; however:^2,3
  • Many patients consider warts unsightly or find them uncomfortable/annoying.
  • Early treatment usually offers the best results.
  • Not treating warts increases the risk of them spreading.
• Warts often disappear without treatment, but the resolution time can be unpredictable. It may take a few months to two years for warts to go away in children, and may take longer in adults (up to five to ten years).^1-3
• Warts can be difficult to treat. Patients must be persistent in their treatment as it can take months of regular treatment before the warts disappear.^3,17,18
• Data are very limited for the treatment of warts.^2,18 Many patients will need to try several treatments or combinations of treatments before the warts resolve.¹⁷
  • Most treatments are off-label.¹⁸
  • Treatments can cause scarring or hypo/hyperpigmentation, especially in sensitive areas or in patients with darker skin types.^2,3,18
  • Treatments can be painful or difficult to tolerate, especially for children.¹⁸

What are first-line treatments for common and plantar warts?

• First-line treatment for warts often involves salicylic acid and/or cryotherapy, as they have the most evidence for efficacy.
• These treatments are sometimes combined to increase efficacy [Evidence Level C].²
• They damage or destroy the infected epithelium, which is thought to induce an immune response that helps to clear the virus and the wart.²

What is the role of salicylic acid for wart treatment?

Topical salicylic acid (e.g., Dr. Scholl’s Clear Away, WartStick, Compound W)

• Concentrations typically vary from 17% to 40%.
  • Higher concentrations are used on thicker skin (e.g., soles of the feet), while lower concentrations are applied to more sensitive skin.²
  • Concentrations above 40% are sometimes prescribed, but these formulations must be compounded.⁵
  • Higher concentrations may be associated with decreased compliance due to increased skin irritation.²
• Various formulations are available (e.g., gel, liquid, ointment, patch, plaster/pad).³
• Check product labeling for specific instructions (e.g., age restrictions, application frequency).^3,6,7
  • Reduce the frequency of application if the treatment site becomes painful.³  
• Increased efficacy compared to placebo (mean cure rates of 49% vs 23%, respectively) [Evidence Level B-2].^1,2,8
• Salicylic acid may be less effective compared to cryotherapy for common warts.²
• Can cause irritation. Avoid in patients with neuropathy or foot ulcers.²
• Sometimes compounded with other topicals (e.g., lactic acid, podophyllotoxin, cantharidin), particularly for plantar warts.² 
• Often combined with other treatments (e.g., cryotherapy).¹⁸

What is the role of cryotherapy for wart treatment?

Cryotherapy is the application of intense cold, by spray or cotton-tip applicator, directly to the wart.

• Most commonly done in a prescriber’s office using liquid nitrogen.²
• Typically, five to 30 second application, done every two to three weeks until the wart clears (for up to six treatments). Techniques and duration can vary among prescribers.²
• The mean reported cure rate is 49% [Evidence Level B-2].^2,8
• Use very cautiously over joints (e.g., digits) due to risks (e.g., severe pain, possible neuropathy).⁵
• Use caution when applying near nails, tendons, and nerves due to the risk of nerve or tendon damage, or nail dystrophy.^2,5
• Can be painful and may cause blistering.^2,5 Adverse effects increase with longer, more frequent applications.² Healing takes four to seven days and may cause scarring.^2,5
• Hyper- or hypo-pigmentation may occur at the application site, particularly with darker skin types.^2,3
• There are also various OTC cryotherapy kits available.
  • Some kits contain compressed-gas devices with propane and/or dimethyl ether² (e.g., Compound W Freeze Off Advanced, Freeze Away Max [US], Wart Freeze [Canada]).
  • Other kits have a pen device containing nitrous oxide (e.g., Compound W Nitrofreeze [US]).
  • Patients should adhere to the instructions included on the product they purchase (e.g., application directions, age cut offs).
  • The temperatures applied to the wart are not as low as with liquid nitrogen, which likely decreases efficacy.²

What are self-care tips for patients treating warts at home?

• Prior to topical treatments, patients should soften the wart by soaking in warm water for five to ten minutes.^2,5
• After soaking, an emery board or sandpaper should be used for paring the wart, or gently removing the upper layers of the wart.^2,4,5
• This removes the dead skin from the surface to help topical treatments better penetrate the wart.
• Do not reuse or share the emery board or sandpaper.
• Avoid pumice stones and similar tools unless they are disposable.
• Protect the surrounding skin during the process to prevent the wart from spreading.

What nondrug remedies or supplements are used to treat warts?

• Duct tape
  • May work by peeling away layers of the wart, irritating the wart to stimulate the patient’s immune response, or raising the skin temperature to inhibit the virus.³
  • Applied over the wart and/or topical therapies. Change with the topical med, or every three to six days if used alone.⁴
  • Studies conflict on efficacy, but use is generally considered harmless.^1,3,9
• Zinc
  • Topical zinc oxide 20% ointment, applied twice daily for up to 3 months seems to have a similar cure rate as ointment containing salicylic acid 15% with lactic acid 15%.¹² Oral zinc has also been used with conflicting results, but may also be effective.^10-12
• There are various supplements and herbal products (topical and oral) marketed for wart treatment. These include mayapple (which contains podophyllum peltatum, the source of podophyllin), greater celandine, bittersweet nightshade, black cohosh, echinacea, garlic, fig sap, oleander, oregano, oral propolis, etc.^2,13 These remedies lack sufficient evidence and are not recommended.¹³
• There are many home remedies that have been used to treat warts. These remedies lack evidence and are not recommended: apple cider vinegar, banana or orange peels, garlic, raw potatoes, etc.²

When should you refer patients for wart treatment?

Patients should be referred to their prescribers if the wart is:

• painful, itchy, burning, or bleeding.³
• quickly multiplying or many warts.³
• on the face or genitals.^3,6,7
• in a patient who is immunocompromised or has diabetes.^3,6,7
• not responding to OTC treatments (e.g., still present after 12 weeks of treatment).⁵

What are other options for difficult to treat or resistant warts?

• There is no clear evidence for treatment choices for difficult to treat or resistant warts.^5,17,18 Combinations of medications with different mechanisms can be tried.^1,17 Topical options may be preferable before trying intralesional injections.
• Some options include:
  • 5-fluorouracil (5-FU) 5% cream (Efudex, etc).^4,9
  • imiquimod 5% cream (Aldara [US], Aldara P [Canada], etc).⁴
  • cantharidin (also called cantharone, or “beetle juice”).^3,14
  • electrosurgery/cautery (burning), curettage (scraping), or excision by dermatologists.^2,3
  • oral H2-blockers (e.g., cimetidine).¹⁷ There are H2 receptors on T-suppressor cells. Blocking the receptors may increase cell-mediated immunity. Randomized trials with H2 receptor antagonists have found no increased efficacy in the treatment of warts over placebo.^2,5
  • other treatments include: silver nitrate, phenol, glycolic acid 5%, pyruvic acid, citric acid 50%, formic acid, laser therapy, photodynamic therapy, trichloroacetic acid, trichloroacetic acid/monochloroacetic acid, anthralin, podophyllin and podophyllotoxin, retinoids, cidofovir, interferon, immunoglobulin, valaciclovir, vitamin D analogs.^2-5,18

What is the role of 5-fluorouracil (5-FU) 5% cream in wart treatment?

5-fluorouracil (5-FU) 5% cream (Efudex, etc)^4,9 is believed to inhibit DNA and RNA replication of the wart.⁹

• Various dosing used in studies. Usually applied once or twice daily, with or without occlusion, for up to four weeks.^2,4
• Evidence of efficacy unclear; limited evidence reports efficacy of 10% up to 57%.^4,9
• Adverse effects can include local irritation, inflammation, ulcerations, contact dermatitis, and photosensitivity.⁴
• Often combined with salicylic acid or cryotherapy.⁴ Has been combined with salicylic acid for the treatment of plantar warts, but required prolonged use (up to 235 days) for efficacy.^2,4
• Parenteral 5-FU has also been used as an intralesional injection.⁴

What is the role of imiquimod 5% cream in wart treatment?

Imiquimod 5% cream (Aldara [US], Aldara P [Canada], etc)⁴ induces interferon-alpha and other cytokines to block viral replication.^2,4

• Approved for genital warts, but not common warts or plantar warts.
• For common or plantar warts, various dosing was used in small studies such as applying once daily, covering with tape overnight, and then repeating application five days per week for up to 16 weeks OR applying twice daily.^2,4
• Efficacy data is conflicting, with resolution rates of 10% up to 80%.^4,9,18 Efficacy seems lower in immunocompromised patients.¹⁸ Imiquimod seems more effective used in combination with other meds 
  (e.g., salicylic acid).¹⁸
• Adverse drug reactions can include erythema, edema, and erosions at application site.⁴

What is the role of cantharidin in wart treatment?

Cantharidin,also called cantharone, or “beetle juice,”^3,14 is a toxin extracted from the blister beetle, acts as a topical keratolytic and vesicant.¹⁴

• Considered a safe and effective treatment for warts [Evidence Level B-2].¹⁴
• In-office application of a thin film of 0.7% cantharidin liquid, covered with micropore tape.¹⁴
  • Blisters form under the wart within a day or so of application.¹⁴
  • About one week after treatment, the prescriber may excise the dead wart.³
  • Can be reapplied every three weeks, for up to four treatments.⁵
• Adverse effects can include pain and hypo- or hyper-pigmentation.¹⁴ There may be local swelling and significant pain. There is also a risk of recurrence of the wart in a circle around the treated wart.¹⁴
• Has been used in combination with salicylic acid, podophyllin, silver nitrate, cryotherapy, etc.¹⁴
• Available in the US as a bulk chemical for compounding.¹⁵ Available in Canada as Cantharone 0.7% liquid and Cantharone Plus liquid cantharidin 1%/salicylic acid 30%/podophyllin 2%.¹⁶
• Low-quality evidence has reported up to 100% efficacy of cantharidin with podophyllotoxin and salicylic acid in the treatment of plantar warts.¹⁴

What are intralesional options for treatment of warts?

• Intralesional immunotherapy with contact allergens (e.g., squaric acid dibutylester [SADBE]; Candida, mumps, or tuberculin antigens).^1-5
  • causes a mild allergic reaction around the wart which may increase the clearance of the wart.⁵
  • very limited data on efficacy.
  • injected intradermally, as superficially as possible, into the largest wart, once every four weeks.
  • efficacy appears to extend to non-injected warts.⁵
• Intralesional bleomycin^1-3
  • has antiviral properties via inhibition of DNA synthesis.⁴
  • conflicting efficacy data compared to placebo.¹ Cure rates reported from 14% to 97%.^4,18
  • injected under the wart.⁴

Does human papillomavirus (HPV) vaccine treat warts?

• HPV vaccine does not target the HPV types that cause common warts.¹⁸
  • HPV vaccine targets select HPV types that can cause genital warts and certain cancers (e.g., anal, cervical).¹⁹
• Large, randomized trials of HPV vaccine to treat common warts are lacking.¹⁸
• There are retrospective reports of extragenital wart clearance after intramuscular HPV vaccine.¹⁸
• It’s too soon to say if widespread childhood HPV vaccines or intralesional HPV injections will decrease extragenital warts.¹⁸