Treatments for verruca plantaris range from cryotherapy to topical immunomodulators to lasers. Offering insights from the literature as well as his clinical experience, this author weighs the efficacy of various options for treating the common presentation of lower extremity warts.
Warts are among the most common dermatologic conditions the podiatrist treats. Plantar warts, also known as verruca plantaris, are caused by the human papillomavirus (HPV), which is a double-stranded DNA virus. All papillomaviruses cause infections in the skin or mucus membranes. Since warts are viral infections, treatment can be challenging. Most podiatrists will voice a level of frustration when treating warts because of the lack of predictability of a given treatment plan. Moreover, recurrence or spreading of warts is not uncommon.
When a patient presents to the office with warts, I have a discussion about the degree of difficulty that we may have in rapidly resolving the wart(s). I explain to the patient that we are treating a skin infection caused by a virus that may be resistant to many of the common treatments that are available. I will generally discuss all of the different treatment options and give more detail on the particular treatments I provide. I tell my patients the reason there are so many treatment options is that nothing works great all of the time.
When one reviews the published literature on wart treatments, our clinical experiences corroborate with the overwhelming conclusion that there is no one “most effective” treatment for warts.
For simplicity, I will categorize the treatment techniques for review. For completeness sake, some of the techniques are historical or have fallen out of favor. These are not in any particular order of efficacy.
What You Should Know About Topical Keratolytics
Salicylic acid is the “workhorse” for most podiatrists and family practitioners. Salicylic acid comes in varying strengths from over-the-counter (OTC) preparations at 17% to physician-only manufactured preparations of 55%. Additionally, a pharmacist can compound higher strengths. Other keratolytics include urea, mono- and trichloroacetic acid and cantharidin (Canthacur, Paladin Laboratories).
Keratolytics are designed to peel off layers of skin. When using the medication on a wart, the wart will shrink in size over time until it is gone. Usually, one performs debridement of as much of the keratosis as possible, subsequently applies the medication and uses an occlusive dressing with moleskin or tape. Only a physician should administer the higher strength acid treatments and two-week treatments are typical to repeat the process until the lesion resolves. For OTC treatments, patients can perform daily application. Encourage debridement with an emery board or pumice stone to help reduce the bulk of the wart.
Cantharidin is derived from a beetle and is commonly referred to as beetle juice. Most of the cantharidin used in the United States is either purchased from Canada where it is manufactured or in the U.S. by a compounding pharmacy. Generally, the recipe includes cantharidin, podophyllum and salicylic acid.
The physician applies cantharidin to the wart and covers it with a Band-Aid or tape. The skin will develop a blistering reaction. The wart or part of the wart lifts off, usually within 12 hours. Multiple treatments may be necessary as is commonplace with all of the keratolytic treatment techniques.
A study by Becerro de Bengoa Vallejo and colleagues reported on the use of cantharidin in a retrospective study involving 144 patients.1 After six months of follow-up, 95.8 percent of patients experienced complete eradication of plantar warts.
How Effective Is Cryotherapy?
Cryotherapy is probably the most common treatment performed by primary care physicians and dermatologists. Only a physician can administer liquid nitrogen in the office. Other commonly used physician products include Histofreezer® (OraSure Technologies) and 1,1,1,2-tetrafluoroethane (Verruca-Freeze®, CryoSurgery, Inc.). Home kits consisting of dimethyl ether and propane are now available for OTC use.
As with any wart treatment, multiple applications may be necessary. Most physicians will have patients follow up weekly for cryotherapy treatments until the wart resolves. Cryotherapy can be painful as it is designed to destroy dermal tissues. Redness and blistering of skin may develop.
A Closer Look At Immunomodulators, Autoimmunization And Immunotherapy
Immunomodulators. Topical immunomodulators are agents that regulate the local immune response to the skin. These modulators may include both immunostimulation and immunosuppression. Some of the commonly used agents include imiquimod (Aldara, Graceway Pharmaceuticals), interferon a, interleukin-12 and tumor-necrosis factor-a. These drugs are also used for other dermatological entities such as atopic eczema, psoriasis, vitiligo and other immune-mediated disorders of the skin.
Imiquimod is FDA-approved for condyloma acuminata, actinic keratosis and superficial basal cell carcinoma. It has been used off-label for plantar warts. It is expensive in comparison to other topical treatments. Imiquimod initiates an anti-viral state by upregulating specific cytokines to eradicate HPV. Most of the literature on the use of the drug for plantar warts is case reports. No large prospective studies have been performed. Skinner stated that imiquimod works better with a combination of cryotherapy, keratolytics and occlusion.2
Autoimmunization. Needling of warts is a technique that can initiate immunization. With the patient under local anesthesia, use a syringe needle to poke through the wart 100 to 200 times. This can push virus particles into the body and mount humoral immunity.
Panacos and colleagues described another technique to excise a wart and implant the wart into the abductor muscle belly.3 This too can initiate an autoimmunization against the virus. This technique may be of benefit for severe cases in which there are large surface areas of skin affected such as mosaic warts.
Immunotherapy. Two of the most common types of therapy include injection of the mumps-measles-rubella (MMR) vaccine and Candida albicans antigen. Physicians have used the Trichophyton antigen in combination with the MMR vaccine and Candida. Like autoimmunization, a treatment of one wart can treat the whole body (or all of the similar warts).
In a study by Gamil and co-workers, the researchers used the MMR vaccine in 23 patients with plantar warts.4 Twenty patients (87 percent) had complete resolution, one patient had partial improvement and there was no response in two patients. One patient experienced recurrence. Side effects included pain during the injection (82.6 percent) and flu-like symptoms (4.3 percent).
Studies have reported that oral agents such as cimetidine (Tagamet, GlaxoSmithKline) and zinc sulphate are effective in the treatment of verruca. Stefani and co-workers compared the two drugs in a double-blind prospective study for efficacy.5 One group took 35 mg/kg of cimetidine and the other group took 10 mg/kg of zinc sulphate. There were nine patients in each group. One patient was lost in the zinc sulphate group due to nausea and vomiting. Five patients in the zinc sulphate group were cured. None of the cimetidine group had a cure. About half of the patients had some improvement.
A study by Glass and Solomon showed an 84 percent clinical improvement or resolution in 20 adults treated with high-dose cimetidine for recalcitrant warts.6 However, Yilmaz and co-workers performed a placebo-controlled, double-blind study including 70 patients with multiple warts.7 The conclusion was “our results show that cimetidine is no more effective than placebo in the treatment of patients with common warts.”
A placebo-controlled study by Al-Gurairi and colleagues showed oral zinc sulphate to be efficacious.8 Each of the 80 patients had more than 15 warts. Forty patients received zinc sulphate at 10 mg/kg and were followed for two to six months. The placebo group received glucose and were followed for the same period. Only 23 zinc-treated patients and 20 placebo-treated patients completed the study. The results revealed no resolution of warts in the placebo group and 86.9 percent of the zinc treated group had complete resolution within two months.
In 1998, Bigby stated that cimetidine has no proven efficacy for the treatment warts.9 Interestingly, in the same article, he purported that silicone gel sheeting and Mederma cream (Merz Pharmaceuticals) have no proven benefit for keloids.
Salient Insights On Using Laser Treatments
There are various types of laser treatments for warts. Pulsed dye laser (PDL) targets the pigments in tissue such as melanin. In treating warts, the laser has an affinity for hemoglobin within the blood vessels of the wart. This will cause the necrosis of the tissue. Sethuraman and co-workers used the pulse dye laser to treat 61 children with recalcitrant warts and reported 75 percent total clearance with an average of 3.1 sessions.10 The overall success rate for resolving plantar warts was 69 percent.
Park and Choi performed a prospective, non-blinded, non-randomized study on 120 patients with warts who were treated with the pulsed dye laser.11 The overall clearance rate was 49.5 percent. Plantar warts were more difficult to treat than flat warts or periungual warts, according to the study authors.
Passeron and colleagues performed a non-randomized, prospective, placebo-controlled, single-blinded study on patients with palmoplantar warts.12 Their conclusion was “PDL appears to be an effective treatment in palmoplantar warts but the efficacy of this method seems to be only equivalent to that of standard treatments (cryotherapy or salicylic acid preparations).”
Carbon dioxide lasers vaporize the wart. In this case, the physician uses a laser like a scalpel to carve out the wart and vaporize the base.
Physicians have used the Er:YAG laser along with light-emitting diode (LED) therapy. Trelles and colleagues reported on 121 warts treated with this method.13 As with the carbon dioxide laser, one excises the lesions and vaporizes them, leaving a wound to heal. The study authors reported 6 percent recurrence at a 21-month follow-up. According to the study, “minimal” scarring occurred and 15 days was typical for healing.
Can Chemotherapy Play A Role In Eradicating Warts?
Clinicians have used virucidal agents such a glutaraldehyde (rarely used anymore) and formaldehyde topically to treat warts. Physicians most commonly use 10% formaldehyde.
Jennings and co-workers compared outcomes of wart treatment in one group using 10% formaldehyde and another group using 10% formaldehyde and monochloroacetic acid.14 The overall cure rate was 61.4 percent with no statistically significant difference in the two groups.
Physicians have also used 5-fluorouracil (5-FU) (Efudex, Valeant Pharmaceuticals), available in both topical cream and injection, to treat warts. The drug inhibits DNA and RNA synthesis, preventing cellular replication of the virus. A study by Salk and colleagues compared 5-FU cream under tape occlusion versus tape occlusion alone.15 They found that 85 percent of the 5-FU group had a sustained cure rate. The average time to cure was nine weeks.
A prospective, placebo-controlled, double-blind randomized trial authored by Yazdanfar and co-workers showed complete wart resolution in 64.7 percent of the group receiving injectable 5-FU and lidocaine with epinephrine.16 This is in contrast with 35.3 percent resolution in the placebo group who received saline injections.
Weighing The Efficacy Of Excision And Occlusion
One can completely excise warts using the 3:1 principle using a double semi-elliptical incision. Remove the skin wedge including the wart and suture the skin. Another common technique is to excise the lesion by excochleation. This technique requires local anesthesia. Use a scalpel to circumscribe the wart but use caution so you do not penetrate into the fatty layer. Proceed to use a curette to remove the wart. One can cauterize the base with a chemical such as phenol or use an electrocautery device such as a hyfrecator.
Another option is occlusion of the wart. Researchers have studied the use of duct tape in comparison to other documented treatments. The theory is that duct tape will suffocate viruses and the high level of adhesive properties of the tape will mechanically remove more warty tissue than other less sticky tapes.
De Haen and colleagues studied duct tape versus placebo in a randomized placebo-controlled trial involving 102 children.17 The placebo group used a corn pad around the wart and the test group used duct tape. Patients underwent both treatments for six weeks. The result was that duct tape had a modest but not statistically significant effect on wart reduction in comparison to placebo.
Other Considerations In Selecting Wart Treatment
There have been various published reports of combination treatments. For example Van Brederode and Engel described combining cryotherapy with 70% salicylic acid.18 The report published favorable eradication rates of 89.2 percent in 86.2 percent of the 29 patients.
Soroko and colleagues reported using 2% salicylic acid through iontophoresis.19 Only one patient out of 19 had resolution and 78.9 percent had reduction in the size of the wart. One patient showed no change and two had an increase in the size of the wart.
A study by Bruggink and colleagues compared treatment with liquid nitrogen versus topical salicylic acid in a randomized controlled trial.20 The first group received cryotherapy with liquid nitrogen every two weeks, the second group applied salicylic acid themselves daily and the third group used a wait and see approach. Of the 240 patients who completed the study, cure rates were 39 percent in the cryotherapy group, 24 percent in the salicylic acid group and 16 percent in the wait and see group. Cure rates among the patients with plantar warts did not differ significantly between the treatment groups.
When you research the different treatment options for plantar warts, you quickly find that there are many contradictory reports and that no treatment is really superior to another. That is what makes the treatment so difficult.
In my practice, I generally provide two treatment options. I use cantharidin as topical treatment and I offer excision techniques. Most of my patients have already tried cryotherapy by their primary care physician and personally speaking, I have not had good results with that technique so I don’t offer that.
My preference is to excise lesions because I know anecdotally that is going to be the quickest way to resolve the condition. Certainly, if there are multiple lesions or mosaic warts, excision of all lesions at one time may not be practical. In these cases, I will tend to stage the excisions over a minimum of two-week periods.
No matter what method you choose to use, it is paramount that your patient understands that you are treating a viral infection that can be resistant to treatment, may take prolonged treatments and may have recurring or spreading of infection.
Dr. Fishco is board-certified in foot surgery and reconstructive rearfoot and ankle surgery by the American Board of Podiatric Surgery. He is in private practice in Phoenix. He is also a faculty member of the Podiatry Institute. Dr. Fishco pens a monthly blog for Podiatry Today. For more info, visit http://www.podiatrytoday.com/blogs/william-fishco-dpm-facfas .
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