It is generally thought that about 50 percent of all warts will spontaneously resolve within six months. However, some warts may remain at the same location with no apparent change for many years and others will continue to spread, expand or enlarge with time. Warts are generally self-limiting and very harmless but may cause symptoms due to the fact that they are unsightly, cause embarrassment, impede function, become irritated or cause pain. Verrucae are commonly termed warts. These are benign intraepidermal neoplasms caused by a variety of different viruses. Papillomaviruses belong to the family Papovaviridae and are species-specific, double-stranded DNA viruses. There are approximately 150 different human papillomaviruses (HPV) that have been implicated in the formation of human warts. The HPV types are listed numerically by their DNA composition for identification purposes. Individual variations in cell-mediated immunity may explain the differences in the size, severity, location and duration of warts. This may also explain why some warts respond readily to simple treatment while others appear to be extremely resistant to most forms of therapy. A Few Thoughts About Differential Diagnosis Clinically, warts obscure the normal visible skin lines and this usually helps to differentiate the wart from other lesions with a similar clinical appearance. Contrary to popular misconception, there are no “roots” penetrating into the dermis or subcutaneous layers. There is, in many cases, a single point in the wart tissue that is thicker or deeper than adjacent wart tissue. This may make the wart appear to be on a stalk or have a deep rooted base, which is probably the source of the mistaken belief in roots. Small thrombosed blood vessels may become entrapped in the cylindrical projections formed by the virus and are seen as small black dots on the surface of some warts. It is not always possible to identify a skin lesion as a wart simply based upon its appearance. The most common group of lesions in the differential diagnosis include: acquired digital fibrokeratoma, actinic keratosis, arsenical keratosis, cutaneous horns, lichen planus, molluscum contagiousum, prurigo nodularis, seborrheic keratosis and squamous cell carcinoma. Many of these lesions require a biopsy for positive identification. How To Differentiate Between Different Warts The most common lower extremity warts are common warts (verruca vulgaris), plane or flat warts (verruca plana), cylindrical (or digitate) warts, peri- and subungual warts, plantar warts and mosaic warts (see “A Review Of Common Lower Extremity Warts” below). Common warts. The common wart starts as a smooth, flesh-colored papule and eventually evolves into a dome-shaped, discolored, thickened growth with hemorrhagic or small thrombosed capillaries. Generally, these warts are few in number and are common on the non-weightbearing surface of the lower extremities. Common warts may range in color from light brown and slightly erythematous to darkly pigmented. They vary in size from 1 millimeter to well over 1 centimeter in diameter and may coalesce to produce larger lesions. Flat or plane warts. Flat or plane warts are also referred to as juvenile warts. They are very small lesions with a slightly raised, smooth, skin-colored or slightly pigmented, flat surface. These flat warts usually do not have the typical rough warty appearance or vascular display of other warts. They may occur along a pressure area or an area that has been scratched (Koebnerized), and are usually multiple and linear in arrangement. You’ll frequently see these warts on the lateral aspect of the foot or ankle. These flat warts are extremely likely to undergo spontaneous remission or involution but may be extremely persistent and unresponsive to therapy. Be aware that if you mistake these lesions for inflammatory conditions and treat them with topical corticosteroids, they will usually spread. Cylindrical warts. These warts, also known as digitate warts, are less common on the foot but you may see them on the toes. They are more frequently found on the face, neck or anogenital region. These growths consist of a few or multiple fingerlike projections that emanate from a single base. They may have visible capillaries within the cylinders that bleed easily with trauma or manual trimming. Periungual warts. Periungual and subungual warts are sometimes more difficult to treat than freestanding warts because of the adjacent or overlying nail plate. When the wart is next to a nail, the localized treatment may cause considerable pain and even a paronychia. These warts also have a strong tendency to spread to adjacent toes, which are sometimes referred to as “kissing warts.” Plantar warts. Any wart found on the weightbearing or bottom of the foot may be called a plantar wart but some, such as the mosaic wart, are usually not referred to as plantar warts. Plantar warts take on a different character because of the pressure and, in many cases, the presence of overlying callus formation. The lesions may be solitary, grouped or multiple in appearance. They are often pale or yellow in color due to the keratin levels or hyperkeratosis present. The multiple thrombosed capillaries are commonly visible in most of the larger lesions and these will bleed upon trimming of the wart. Mosaic warts. Mosaic warts, sometimes referred to as myrmecia, are generally a coalescence of several smaller warts or grouping of clusters that form a large plaque. Mosaic warts are usually irregular and contain multiple cores that have coalesced. This results in variable depths of the lesions with one area of the plaque that is usually much deeper than adjacent wart tissue. This lesion typically bleeds freely when you shave it or trim it due to the large numbers of small looping capillaries that are present. Due to the increased size and multiplicity of this type of wart, treatment can be very difficult and may require repeated attempts to resolve the lesion. These larger lesions may be found on any body surface and are not necessarily found on weightbearing surfaces. Mosaic warts may become very thick and dry. They can crack open with deep fissures that lead to increased discomfort. When you see them on the direct pressure bearing surfaces of the feet, keep in mind that they may also be painful and interfere with normal gait. One may also see large crecentic or irregular-shaped mosaic warts among patients with acquired immunodeficiency syndrome. These are sometimes referred to as summary warts. Pertinent Treatment Considerations Barring remission of wart tissue, the primary goal of wart treatment is to rid the patient of all visible lesions. Since warts are intraepidermal in nature, you should ensure that any treatment you use does not penetrate into or damage the underlying dermal layer of the skin. However, once the patient has been infected with the human papillomavirus, he or she is more likely to be reinfected again in the future. While there is a wide array of treatment options, there is no one treatment that is completely satisfactory for consistent usage. Choosing appropriate treatment depends upon the type of wart, its location and size, and the age of the patient. When you are treating children, the simplest and most innocuous treatments are recommended due to the high rate of spontaneous regression of warts and the ease of resolution with just about any form of treatment. When you are treating more resistant lesions or the warts of older patients, the treatment may need to be more aggressive in nature. Essential Pointers On Topical Acids Keratolytic therapy is the principal treatment for warts. Topical acids are considered effective and relatively benign forms of treatment for most warts. This treatment relies upon chemical debridement of the epidermal layer of the skin. You may find salicylic acid in 15, 20, 40 or 60% concentrations in a variety of vehicles including flexible collodion, polyacrylic solutions or plaster pads. Be advised that liquid or ointment acid treatment requires persistent application and attention. You would apply salicylic acid over the debrided wart tissue and occlude it with adhesive tape or moleskin. I recommend using the lower percentage in children and the higher doses in resistant warts or older patients. Remove the bandage in 24 hours and proceed to debride the white, macerated tissue to firm or pink underlying tissue. Then the patient would reapply the acid and a new cover, repeating the process until there is resolution of the wart tissue. The patient may experience tenderness or inflammation of the skin adjacent to the wart and this may necessitate periodic intermission of treatment. Given the duration needed to remove wart tissue completely, there may be a compliance problem with some patients. The process of topical salicylic acid treatment is enhanced when you employ pre-packaged plasters, which may range from 15% to 60% concentrations. This method is easier and cleaner for the patient to perform at home. The patient would simply cut the acid plaster sheet to the exact size of the lesion, apply it and secure with tape or moleskin. Emphasize to the patient that he or she should ensure the acid plaster remains over the wart and does not slip onto normal skin. The patient should remove the plaster and any accompanying dead or macerated tissue within 24 to 48 hours. Then the process is repeated until the wart is gone. Keep in mind that similar treatment with other keratolytic liquids and creams containing lactic acid and salicylic acid produces a slightly more intense reaction. These patients may need closer monitoring so you may want to encourage occasional visits to the office. Exploring Chemotherapy Options Chemotherapy is similar to keratolytic therapy and it has also been successfully used for treating warts. Several applications may be necessary and because of the intense reactions, it is advisable to see the patients regularly. Monochloroacetic acid, bichloroacetic acid, cantharidin, podophyllin, formalin, squaric acid and phenol have all been used in the past. Mono- and bichloroacetic acids work in a similar fashion. The wart is trimmed or shaved, the surrounding normal tissue is protected with petroleum jelly and the entire surface of the wart is painted with the acid. The area is then covered with a protective bandage or moleskin and examined in five to seven days. The process is repeated as needed. Formalin is still being used to treat warts and one may consider it for resistant lesions that have failed to respond to more conventional treatments. The technique involves trimming the overlying tissue and painting the wart completely with concentrated formalin solution, and covering the area. This process is repeated weekly. Due to sensitization, it is common to use a 40% diluted solution rather than the concentrated form. Another method is using a dilute 10% solution that the patient applies directly to the warts each night with a roll-on applicator bottle. Alternatively, the patient may soak the entire foot for 20 to 30 minutes daily in a 3 to 4% formalin solution. However, let patients know that sensitization to formalin may still occur with this technique. Excessive drying or thickening of the skin and areas between the toes may occur with the soaking techniques. Patients may need to protect these areas with petroleum jelly prior to soaking. Squaric acid dibutylester, a topical allergen, is sometimes listed in with the chemical therapies even though it is technically a sensitizing agent. The patients are sensitized to a 2% solution of squaric acid in acetone. Then you would treat the warts with a 0.1% application once a week to maintain a mild contact dermatitis. Be aware that this technique is time consuming and has a risk of severe skin reactions. Unlike dinitrochlorobenzene (DNCB), it is not a mutagen and therefore may be a safer alternative. It is recommended that only practitioners who are familiar with its application and side effects use squaric acid. Phenol has been used in a similar method to monochloroacetic acid with comparable results. Phenol causes more allergic reactions, is less predictive than many other topicals and is generally not favored for the primary treatment of warts. However, it is frequently utilized to paint the area of a wart after other acids or treatments have removed the majority of abnormal tissue. How To Get Results With Cryotherapy Cryosurgery with carbon dioxide snow or liquid nitrogen destroys the epithelium through single or multiple freeze-thaw cycles. Necrosis occurs via ice formation, cellular dehydration and, ultimately, through vascular stasis. Be aware that using cryotherapy on the plantar aspect of the foot may cause a deep and painful blister that is very slow to heal. Multiple light applications of freezing are less likely to cause problems than are single aggressive applications. As far as the treatment process goes, you would treat the wart(s) (with or without anesthesia) with the cryoprobe, applicator wand or cotton swab until the entire lesion is frosted white. Immediately after the cryotherapy, the wart blanches. Then allow the tissue to slowly thaw. This produces an inflammatory response and you would then proceed with additional light freezing again. The depth of freeze is generally about 1.5 times the lateral spread. You would repeat this process two or three times on each visit. Several days after the visit, the tissue will blister. Sloughing usually occurs in one to two weeks. During the treatment process, the patient may complain of intense burning but most adults can tolerate the therapy. Children do not fare well with this approach and it is not generally recommended for pediatric warts. A Closer Look At Antineoplastic Agents Intralesional bleomycin sulfate is an effective method of treatment for periungual warts and an alternative method for resistant plantar and mosaic warts of the lower extremities. You would inject bleomycin in a concentration of 1 unit/ml. No more than two units should be injected as a total cumulative dose. One would inject a volume of 0.1ml into warts measuring less than 5 mm in diameter and inject 0.2 ml into warts greater than 5 mm in diameter. This treatment may be very painful but is generally well tolerated by adults. When warts respond, they will usually show hemorrhagic eschars and will blacken and slough during the week following treatment. A second injection may be necessary at the one-month interval. One or two injections is usually all that is necessary to resolve a wart with this technique. One of the problems with this technique is the cost of the product. It is not provided in a multidose vial and is considered to be unstable after approximately 12 hours. Therefore, each treatment requires an additional new vial, which is expensive and inefficient. An alternative method to injecting bleomycin involves applying a solution of bleomycin 1 mg/ml onto the wart and pricking the wart multiple times with a small needle. Patients may tolerate this technique better than the injection method. Another treatment option is 5-fluorouracil (5-FU), a fluorinated pyrimidine that causes necrosis of proliferative tissue. Excessive sloughing and erosion may occur if too large an area is treated or if too much 5-FU is used. Systemic toxicity is also possible. Daily topical application of small amounts of 1% 5-FU for one week is effective (> 50%) in treating single warts. Performing intradermal injections of 0.1 to 0.4 ml 5-FU, depending upon the size of the wart, has shown greater than a 90 percent cure rate. This is an effective procedure. However, several cases in my series showed excessive hyperpigmentary changes in the area immediately surrounding the infiltrative injection sites. These changes all resolved with time. However, you should forewarn the patient of the possibility for cosmetic reasons. A Few Thoughts About Immune Response Modifiers Imiquimod 5% cream is a novel immune-response modifier that has no direct antiviral activity but cell-mediated immunity at the site of application appears to be the primary reason for wart regression. The topical cream is believed to act by up-regulating interferon and stimulating other cytokines involved in the cell-mediated response. These cytokines affect cell growth and differentiation, and may also induce the synthesis of other proteins that may be, in part, responsible for antiviral activity. Both interferon and cytokines activate natural killer cells that target tumor and virus-infected cells. I have been using imiquimod 5% cream for resistant warts in two different ways. When treating smaller warts or the presence of several warts, I have patients apply a very small amount of the cream to each wart daily after showering or bathing, and encourage them to rub it in completely. I do not have the patients cover the warts. When treating larger or mosiac-type warts, I debride the wart to pinpoint bleeding, apply hemostatic agents and a small amount of imiquimod cream, and cover the area with moleskin or adhesive tape. The covering is removed in five to seven days and the process is repeated. My success rate with this approach is about 70 percent at 14 weeks of therapy. The side effects include itching and burning at the application site. Also be aware that repeated daily application may lead to adjacent skin reactions. All symptoms subside upon discontinuing the medication. Interestingly, studies have shown that skin patch testing with imiquimod, the cream vehicle alone and with commercial skin lotion found that the skin lotion was more irritating than imiquimod or the vehicle cream. Can Electrodesiccation Have An Impact On Single Warts? Combining electrodesiccation with curettage is an effective method for removing small, single warts. The electrodesiccation technique involves using a hyfrecator unit with a needle tip applicator on a hand-held instrument. You would anesthetize the wart area with local anesthetic and prep the surrounding area. Proceed to advance the current until a visible spark occurs between the instrument tip and the wart tissue. The wart area is lightly charred and you can curette the residue away. The wart will become firm and it is possible to completely remove the wart base intact. You may apply additional hyfrecation to the underlying base to reduce any residual verrucae tissues that might be present. Then you would treat the area much like any other wound or minor burn until it is healed. A Primer On Performing Blunt Dissection Blunt dissection and curettage is one of the most consistent and effective methods of removing lower extremity warts. This simple surgical technique is fast and usually non-scarring as long as you avoid penetrating the underlying dermal skin layers. The technique begins with local anesthesia with epinephrine delivered around and under the involved wart. One technique involves using a jet injector to administer a small amount of lidocaine at the four corners surrounding the wart. You may then perform additional infiltration from these anesthetized skin areas. Proceed to establish a plane of dissection with tissue nippers, dissection scissors or a small surgical blade. This outer cut should extend through the epidermal layer only and should not involve the dermis if possible. Once you’ve established the plane of the wart by cutting the skin circumferentially outside the wart capsule or lining, insert the blunt dissector (or end of a small curette) in the plane of cleavage and gently separate the wart from the underlying normal dermal layer. Make short, firm and even strokes that will ‘push’ the wart tissue off in a single unit. Once you’ve removed the wart from the area, perform light curettage of the base to smooth any rough spots and remove any residual wart tissue that may remain on the dermal layer. Using a scalpel technique, trim the outer edge of the crater resulting from the wart removal. This creates a very shallow crater that seems to greatly enhance the speed of healing. Lightly coagulate bleeding areas with the hyfrecator or with the topical Monsel’s solution. Proceed to paint the exposed area with a fluorinated corticosteroid cream and cover it with non-adherent gauze and mildly compressive bandage. See the patient in three to four days for a follow-up visit. At this visit, change the dressing and apply the steroid cream once again. You should then see the patient one week following surgery and after all dressings have been removed. Subsequently, the wound should remain exposed, unless it is in a weightbearing location, and one should emphasize warm water Epsom salts soaks until healing is complete in two or three weeks. This combination of blunt dissection (exchocliation), curettage, and topical steroid under mild compression has provided the highest long-term success for the resistant plantar verrucae in my practice. Final Notes There are a variety of other treatments ranging from intralesional interferon alpha and photodynamic therapy to flashlamp-pulsed dye lasers and retinoids. However, there is no consistent evidence in the literature to justify using most of these modalities on a routine basis. There is also no reason to believe that these methods are safer or more effective than the common treatments with salicylic acid, formalin solutions or blunt dissection and curettage techniques. Pedal warts can be very frustrating because of the many different types of warts and variety of viral causes. Warts do not consistently respond to any given treatment program and this causes difficulty in forming a good predictive response. When a patient presents with warts that have never been treated in the past, I will usually start therapy with a combination of oral vitamin A plus zinc tablets (one tablet twice a day for 30 days). Then I’ll follow this with local debridement and topical salicylic acid or topical formalin solution with tape or moleskin occlusion. If this process is not successful within about four weeks, I will proceed to other forms of treatment. When a patient presents with warts that have already undergone therapy, I will consider using a combination of treatments that have not already been done. This might also include the use of vitamin A plus zinc, topical 5% imiquimod cream, local debridement, tape covering or other options. When the wart appears to be much more resistant to therapy, I will consider the blunt dissection and curettage treatment. While the blunt dissection and curettage technique of wart removal is more aggressive, I have found it to be one of the most consistent treatment forms with one of the best predictive values and the highest long-term success rates for resistant warts. Given the fact that it’s a more aggressive approach, I do not use it at all in children and it should not be used as a first-line of therapy for warts in adults unless all other, more conservative methods have already failed. Dr. Dockery is a Fellow of the American Society of Podiatric Dermatology and the American College of Foot And Ankle Surgeons. He is Chairman of the Board and Director of Scientific Affairs at the Northwest Podiatric Foundation for Education and Research in Seattle.
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