Warts are common benign skin tumors caused by viral infection of localized areas of the epidermis. By an unknown mechanism, the virus stimulates the infected cells to proliferate so that the epidermis becomes thickened and keratotic. The associated dermal papillae become elongated. The capillaries within them are frequently thrombosed. These are the brown-black specks often seen in warts. The wart virus is a papova (papilloma, polyoma, and vacuolating) virus. It is 38 µm. in diameter, contains DNA, and replicates in the host cell nucleus. It is remarkably stable under a variety of laboratory conditions. To date, attempts to grow the virus in vitro have been unsuccessful, and no reliable serologic procedure for the immunologic identification of the virus has been developed. It is not known whether the various clinical types of warts are caused by the same agent or by a group of closely related viruses. Flat, common, and moist warts seem to be caused by the same virus. When a cell- and germ-free filtrate prepared from moist warts is inoculated into dry skin areas, common or flat warts will grow. If the same extract is inoculated into mucous membranes, moist warts will develop.
Figure 1. Multiple common warts.
Warts occur in 5 to 10 per cent of children, the greatest total incidence being around puberty. Common and plantar warts are more prevalent in girls; flat warts (before puberty) are more common in boys. Plantar warts are rare below the age of five. After the age of 20, the incidence of warts in men and women is equal. They are less common in adults, possibly because of the development of immune resistance. Clinical experience supports the popular belief that warts are transmitted by contact. A child, chewing on a wart on his fingers, can inoculate warts onto his Ops and tongue. Warts can grow in a line along a scratch or be spread by shaving (autoinoculation imitating the Koebner phenomenon). Moist warts (condylomata acuminata) are frequently, but not always, transmitted by sexual intercourse. In experimental subjects injected with filtrates of wart-infected tissue, it has been shown that warts can be inoculated from one site to another on a person and from one person to another. The incubation time was one to several months. Many subjects were not inoculable.
Warts are an example of a "conditioned" infection. Mere contact of virus and host is usually not enough to produce disease. Other factors influence the likelihood of infection. Traumatized skin, thickened epidermis, hyperhidrosis, and certain hormonal states (puberty, pregnancy) seem to potentiate the infectivity of the virus. Untreated, most warts will spontaneously involute after approximately two years. Some warts, however, will persist for many years. The involution of some of the warts is probably on an immunologic basis. Lacking a laboratory model, this cannot yet be confirmed. The clinical evidence for a role played by the immunologic system is strong. Warts occur predominantly in children. Many adults cannot be inoculated with wart virus preparations. Diabetic patients who have impairment of delayed hypersensitivity and Chemotaxis may have multiple warts. In patients who are immunosuppressed, warts may sometimes proliferate wildly.
CLINICAL APPEARANCE AND DIFFERENTIAL DIAGNOSIS
The large majority of warts are Verrucae vulgares, common warts. They are flesh-colored to grayish-brown firm papules or nodules with characteristic horny pitted surfaces (Figure 1). Brown or black specks may be seen beneath the surface, particularly after paring. These are the thrombosed dermal capillaries. Intact capillaries are the source of the small bleeding points encountered when paring. These warts are usually 1-10 mm. in size, but they may grow or become confluent to form lesions 2 cm. or more in diameter. They occur most often in children. They are most commonly found on the dorsa of hands and fingers but can grow anywhere. They are most troublesome when they grow under and around the nails (periungual and subungual Verrucae) (Figure 2) and in these locations must be differentiated from periungual fibromas in tuberous sclerosis. Also included in the differential diagnosis of common warts would be keratoses and other fibromas.
Filiform warts have one or more slender fingerlike projections 2-10 cm. long on a narrow base. The projections have some cornification but are not as hard and hornlike as "cutaneous horns." They are found most frequently on the face and neck of young adults and at the corners of the mouth in older persons. Besides cutaneous horn, the differential diagnosis would include nevi and fibromas.
Figure 2. Periungual wart.
Figure 3. Rat (juvenile) warts on the face.
Figure 4. Rat warts on the hand.
Figure 5. Mosaic plantar wart.
Flat warts (Verrucae planae) are flat-topped, round, slightly raised, 2-6-mm. tan to yellow-pink lesions with a granular surface (seen best with a magnifying lens). They occur most commonly on the face and dorsa of the hands (Figure 3). They also occur on the extensor surfaces of the arms and legs (Figure 4). They can be quite numerous, even confluent. At the periphery of confluent areas, one can find the typical small, flat individual lesions. The lesions can sometimes look irritated and be quite itchy. The differential diagnosis includes lichen planus and nevi.
Plantar warts are warts on the soles. They often occur in areas of thick callus. Hyperhydrosis seems also to be a potentiating factor. They are usually flat, since pressure causes them to grow peglike into the tissue. They are often very painful. Multiple confluent warts are called mosaic warts (Figure 5). They can occur on the fingers as well as the soles. The wart has sharp margins where the normal skin ridges stop or are diverted, like a rock in a stream. In simple calluses, the skin ridges are not distorted. Paring the warts may reveal the characteristic brown specks. Corns look like simple calluses but are painful. When a corn is pared, a small, firm, translucent particle is found at the base overlying tender pink skin. Also included in the differential diagnosis are a foreign body (splinters, glass, etc.), neurofibroma (rare), and a painful scar. The last-mentioned lesion might be difficult to separate from plantar warts, especially if the scar were secondary to previous treatment attempts. A stippled surface and bleeding points would indicate that the wart was still present.
Moist warts (condylomata acuminata, venereal warts) occur on the genitalia and around the anus (Figures 6 and 7). They can also occur, though uncommonly, in the toe webs, in the mouth corners, and on the palpebral and bulbar conjunctiva. The lesions are reddish pink to white, luxuriant in growth, and frequently comparable with a cauliflower in appearance. If they extend onto adjoining dry skin, they will assume the appearance of common warts. Condylomata accuminata must be distinguished from condylomata lata. If there is any doubt, dark-field examination and serologic testing should be done. Condylomata acuminata have been reported to undergo malignant degeneration and so must be followed carefully. The agent most frequently used for therapy of moist warts, podophyllin, is similar to colchicine and causes bizarre nuclear change. If a biopsy is done after podophyllin treatment, the pathologist should be aware of the previous treatment.
Figure 6. Condylomata accuminata in a child of three years.
Figure 7. Condylomata accuminata in an adolescent.
There are a few general principles to keep in mind when treating warts. The reasons for treating warts are to prevent further dissemination, to relieve pain (especially with regard to plantar warts), and to improve the patient's appearance. Most warts will spontaneously involute after one to two years. Even if a wart is resistant to therapy, one ought not be provoked into desperate measures, for the simple passage of time may result in a cure. The wart virus is limited entirely to the epidermis. Treatment limited to this level ought not to result in any scarring. Discomfort should be kept to a minimum. There is no specific treatment for warts. Systemic treatment and vaccines have been ineffective and should not be used. The mode of therapy is determined by the type of wart, the site, and the patient's response to treatment. Warts should be carefully pared before each treatment.
One mode of therapy that has been used for all types of warts is psychotherapy (including hypnosis, folklore spells, etc.). The amount of success has ranged from spectacular to none. Some argue that supposed cures merely coincide with the time the wart would naturally have undergone resolution. However, the rapidity with which the warts have resolved immediately following such therapy in some instances would argue for some therapeutic effect.
Figure 8. Method of applying liquid nitrogen.
Figure 9. Frozen wart with 1-mm. margin
Figure 10. Appearance three days after freezing.
A simple and effective treatment for verruca vulgaris and digitate warts is cryotherapy with liquid nitrogen. An applicator is made by wrapping cotton loosely around a wooden stick or ordinary cotton swab (the cotton on these being too tightly wrapped). This is dipped into the container of liquid nitrogen and applied to each wart for 15 to 60 seconds, depending on the size and location of the warts (Figure 8). There should be a border approximately 1 mm. wide of normal tissue frozen white (Figure 9). No anesthesia is used. There is usually a moderate burning sensation during treatment but a more painful throbbing a few minutes after the treatment is completed. Several hours to a day later, a blister often develops that may become hemorrhagic (Figure 10). This should be left intact unless it is very uncomfortable. If it is, the blister should be drained but the roof left intact. The wart in the roof will dry up and come off as the underlying skin heals. No dressing is needed except to protect the area from trauma. The lesion should be cleaned daily with alcohol or soap and water. Do not freeze directly over a spot where a peripheral nerve comes near the surface (e.g., median nerve). Freezing the nerve may result in peripheral neuritis.
Cautery or electrodesiccation may be used for one or a few common or digitate warts. Anesthetize the wart at the base by injecting intracutaneous local anesthetic. Heat the cautery or desiccator tip to a dull red. Apply it to the wart near the base. This produces bubbling (steam), which helps to separate the wart from the skin. Repeat this around the base of the wart. Remove the burned tissue with a curet. Trim the edges of the wound with scissors. There should be a clean base with little bleeding, which can be controlled with pressure or Monsel's solution.
An effective treatment for common warts, especially periungual warts, employs cantharidin. A 0.1 per cent solution in acetone-collodion 1:1 is applied with a fine-tipped applicator (e.g., a toothpick) to the wart. After it has dried, the wart is covered with a piece of waterproof tape cut to the size of the wart. The hole is covered with a Band- Aid. After one week the dressing is removed. The treated area is soft and separated from the adjacent skin. Debride the area with scissors. If wart tissue remains, repeat the application. If pain develops, remove the dressing at once. One major complication of this procedure is the development of a ring of warts around the treated site.
One problem with the modalities described so far is that they are all more or less painful. Keratolytics work more slowly, are sometimes tedious to apply, and require more diligence and cooperation from the patient but are usually not painful. In general, occlusion will increase the effectiveness of these destructive chemicals by providing moisture for a solvent (by reducing evaporation) and by keeping the medicine in place. Sometimes simple occlusion alone with Elastoplast or Blenderm is curative. Salicylic acid - 20 to 40 per cent in collodion, ointment, or plaster - applied daily with weekly paring, is often effective in treating common warts, including periungual warts and sometimes plantar warts. Periungual warts can also be treated with the modalities described earlier, but caution must be exercised when treating the base of the nail. If the nail matrix is scarred, the nail will be permanently deformed. Lactic acid, 10 per cent in a cream base, or formaldehyde, 8 per cent in collodion or 20 per cent in Aquaphor, applied daily with weekly paring, is also helpful. Patients should be cautioned about the possibility of developing an allergy to formaldehyde. Tri-, di-, or monochloracetic acid can also be used.
Flat warts respond very well to the twice-daily application of 5 to 10 per cent benzoyl peroxide to each lesion.
They usually clear in two or three weeks. Double-strength Whitfield's ointment with or without sulfur added, applied daily, is also effective, as is retinole acid, 0.05 per cent cream, applied daily. Liquid nitrogen can be used with a fine-tipped cotton applicator for 10 seconds to each lesion or "brushed" over larger areas with a larger applicator if there are hundreds of lesions. One complication from this mode of treatment is spotty hyperpigmentation, especially in dark-skinned persons. Light electrocautery or desiccation for a fraction of a second can be used but is moderately painful.
Plantar warts are among the most difficult warts to treat. Excision should not be used, nor should any other treatment that could lead to scarring. X-ray therapy, once used frequently for plantar warts, is generally not used today and should particularly be avoided in children. Liquid nitrogen therapy is not successful. Hyperhidrosis is frequently associated with multiple plantar warts. Application of a 5 to 10 per cent gluteraldehyde solution or a 10 to 15 per cent formalin solution will decrease sweating and often lead to the resolution of the warts. An alternative would be to soak the feet 10 minutes a day in a solution of formaldehyde USP diluted 1 teaspoonful to 1 quart of water. This must be done for three to four months, with only brief interruptions if the feet become too dry and fissured. Again, the problem of contact sensitization may occur. If it does, this mode of therapy must be discontinued. Salicylic acid plasters, 40 per cent, can be cut to the size of the wart, applied, and occluded with waterproof tape. This is changed every three days and the wart pared weekly. Even if the wart persists, the patient usually experiences relief from pain, as much of the excess keratin is removed.
There are many combination therapies for the treatment of plantar warts. Two such regimens will be outlined here.
1 (Blank). With a wooden applicator apply phenol to the wart, then apply nitric acid. This reacts with the phenol and produces a dry eschar. A firm felt ring (e.g., corn pad) is applied over the wart. Then 60 per cent salicylic acid in petrolatum is placed in the hole over the wart. The pad is taped firmly in place and kept dry. This is repeated every five to seven days. If it becomes too painful, omit the first part but continue with the pad and the keratolytic.
2 (Montgomery). Apply trichloroacetic acid to the wart (or area if treating mosaic warts). When the lesion is moistened, rub the area with a silver nitrate stick. Apply a salicylic acid plaster, cut to the size of the area, and tape firmly in place. Repeat every five to seven days, omitting the trichloroacetic acid if the lesion becomes too painful.
Sometimes orthopedic management with special shoes, metatarsal bars, etc., to keep weight off the wart, is necessary to cure chronic cases.
Condylomata acuminata are usually treated with 20 per cent podophyllin in tincture of benzoin. The surrounding normal skin should be protected with petrolatum. The application should be allowed to dry for a few minutes. The patient should be carefully instructed to wash off the medication thoroughly in four to six hours. If this is not done, marked inflammation, pain, and even sloughing of tissue may occur. Treat only a few lesions at a time. If a large area is involved, treat only part of the area at each visit. The treatment should be repeated weekly. It should not be used near the eyes or in pregnant women. There have been rare reports of neurotoxicity following the topical application of podophyllin. Sometimes, with persistent perianal warts there are rectal warts (visualized with a proctoscope), which must be treated with electrocautery before cure can be achieved. Some intravaginal warts respond to triple sulfa or sulfonamide-urea inserts. If a patient has a sexual partner with venereal warts, that person should also be treated. Cryosurgery or electrode siccation can be used in patients unresponsive to podophyllin.
Because of the apparent relationship between immunologic reactivity and the resolution of warts, attempts have been made to stimulate immune response in patients refractory to other modes of therapy. Patients have been sensitized to DNCB, and then DNCB has been applied to the individual lesions. Results so far have been good, but this form of therapy is still in the experimental stage. Several agents increase immunoreactivity - BCG, levamisole, thymosin, and transfer factor. There have been early reports that levamisole produces regression of warts. Transfer factor from a patient with recently healed warts produced remission in a patient with WiskottAldrich syndrome; but in a doubleblind study of patients with warts treated with transfer factor, those who responded rapidly were evenly divided between the placebo- and the transfer factor-treated groups. Recently Pyrhönen and Johansson reported finding complement fixation antibodies in patients with rapidly healing warts.
Warts are common skin lesions caused by a papova virus. Their clinical appearance is variable. There is no definitive therapy. Therapy must be individually modified to get the best result with the least discomfort to the patient. Most warts will spontaneously resolve after an average of two years, so any therapy that has serious side effects or results in scarring should not be used. New modes of therapy, particularly immunotherapy, look promising but are still in the experimental stage.
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