Warts:

Nongenital cutaneous warts--that is, common, plantar, filiform, and flat warts--are manifestations of the human papillomavirus (HPV).¹ These warts are among the most common dermatologic complaints seen in primary care practices and are among the most common lesions treated by dermatologists.^1-3

Warts occur in up to 10% of children and young adults, most commonly in those between the ages of 12 and 16 years. The age of peak incidence is 13 years in girls and 14.5 years in boys.⁴

Warts are not simply a cosmetic problem. A 9-month prospective study of 85 children and adults with common and plantar warts revealed that 81.2% were embarrassed by the growths; 70.5% were concerned about negative appraisal by others for having them; and 24.7% said that it was difficult to participate in sports because of their warts.⁵ The warts caused moderate to severe discomfort in 51.7% of participants and moderate to severe pain in 35.4%. In addition, treatment resulted in scarring in 19.5% of participants.⁵

Warts sometimes continue to grow in size and increase in number. Warts that do not abate with time or treatment appear to become more resistant. Children with treatment-resistant warts may be reservoirs for HPV transmission.¹

Although warts can spread, they may disappear as well. Warts often resolve without treatment.¹ One review of the natural progression of these lesions found that they spontaneously clear after 2 years without treatment in 40% of children.⁶ In the 9-month study mentioned above, 31.8% of the participants had at least one wart regress spontaneously.

The treatment of nongenital cutaneous warts poses a therapeutic challenge. No single therapy achieves complete remission in all patients.¹ The cornerstones of treatment are cryotherapy and salicylic acid.⁷ Other options include electrodesiccation, laser therapy, topical 5-fluorouracil, intralesional interferons,intralesional immunotherapy, photodynamic therapy, and surgical excision.^8-11 In this article, I review the treatments most commonly available to and used by generalists (Figure).

CRYOTHERAPY

Cryotherapy with liquid nitrogen may be used on any type of wart. Scarring and pigment alterations may occur with this treatment. Liquid nitrogen was found in one study to be equally effective whether applied with a spray gun (cryostat unit) or a large cotton wool bud.¹² In my experience, however, application with a cotton wool bud does not produce optimal freezing, so I use it only in patients who prefer it or who have a very low threshold for pain. Patients should be informed that a spray gun applies more liquid nitrogen to the skin than a wool bud and hence is more painful.

Liquid nitrogen is optimally applied for 10 seconds at a time; this is thought to be more effective than shorter applications.¹³ However, briefer applications may be effective as well. For plantar warts, the recommended treatment is 2 freeze-thaw cycles. In one study, a single application generally sufficed for hand warts.¹⁴

I recommend that patients return for follow-up at least once a month and as often as every week. This increases the likelihood or, at the very least, the speed of treatment success.¹⁵

A useful adjunct to cryotherapy is to pare warts before freezing them, which decreases the temperature to which cells are exposed, thereby increasing the lysis of infected cells. Many clinicians, however, elect to omit this step.Possible reasons for not paring warts include the fact that the procedure is time-consuming and requires a scalpel, which some patients find frightening. Moreover, paring may induce bleeding. In one study, paring before freezing in 2 freeze-thaw cycles improved the cure rate for plantar warts but not hand warts.^16,17

I generally use a 15 scalpel blade; a 10 blade may be required for very large warts. I try to pare the warts down just to the point at which bleeding occurs, because this removes epidermis infected with HPV. Because there are no nerve endings in the epidermis, paring just this layer does not induce pain. However, paring may induce profuse bleeding, largely because warts contain an increased number of blood vessels.

SALICYLIC ACID

Salicylic acid is effective for common and palm or plantar warts. Liquid, adhesive strip, or gel vehicles may be used; the highest concentration of salicylic acid is preferred. Over-the-counter preparations contain less than 17% salicylic acid, whereas physician-prescribed preparations contain as much as 70% salicylic acid.¹ The patient may apply salicylic acid during the day and pare the warts with a pumice stone at night or apply the salicylic acid at night and pare the warts in the morning. Adverse events with this agent are rare. Salicylism (salicylate toxicity), an extraordinary occurrence, is characterized by tinnitus, vomiting, tachypnea, and acid/ base disturbances.

The effectiveness of salicylic acid has been widely documented.¹ A Cochrane review concludes that topical therapy with this agent is safe and effective and that no other therapy has a higher cure rate or fewer adverse effects.¹⁸ Pooled data from 6 randomized clinical trials demonstrated a cure rate of 75% in persons treated with salicylic acid compared with 48% in the control group, who received no treatment.¹⁹ The authors of this study recommend that salicylic acid be used as first-line therapy for flat warts on the face, plantar warts, and flat and common warts on the hands. I do not recommend using salicylic acid on the face.

Some patients inquire about duct tape, which is sometimes applied to warts instead of or in addition to cryotherapy or salicylic acid. I have generally not had good results with this treatment, although others have reported success. In one study of 51 patients, 26 (51%) were treated with duct tape and 25 (49%) with cryotherapy. Warts resolved completely in 22 patients (85%) in the duct-tape group and 15 patients (60%) in the cryotherapy group.²⁰

OTHER TREATMENT OPTIONS

If treatment with cryotherapy and salicylic acid is unsuccessful after 4 or 5 attempts, other options may be offered. Noninvasive therapies include Candida antigen (see below) or dinitrochlorobenzene (DNCB)/squaric acid. DNCB/squaric acid is first applied in a small dose to generate an immune reaction. This is followed by an application to all warts, which may lead to an infiltration of immune cells that have responded to treatment and that will presumably attack infected wart cells. Surgical options include electrodesiccation and laser treatments; however, these therapies sometimes leave scars.

Electrodesiccation. I have successfully used this procedure to treat warts that do not respond to cryotherapy. I desiccate at a low voltage and then perform curettage. The treatment is generally repeated for 2 or 3 cycles at each visit.

Laser therapy. Treatment with a vascular lesion laser, also known as pulsed dye laser therapy, can selectively target hemoglobin contained in blood vessels within the wart.¹ As the hemoglobin heats up, thermal energy is disseminated to surrounding tissues, which cauterizes the blood vessels. The result is a necrotic wart that eventually sloughs off. With a pulsed dye (485 nm) laser, I use a spot size of 10 mm, energy density of 8 J/cm², and pulse duration of 450 microseconds.^21,22

Photodynamic therapy is another option. During this procedure, a photoactivated substance such as levulinic acid is applied to the affected area, which is then exposed to specific light spectra (usually blue). The cost of this therapy prevents widespread use. Laser and photodynamic therapy are generally no more effective than electrodesiccation or cryotherapy, which are much less costly.

Other topical therapies. If patients do not want to try electrodesiccation and are frustrated with cryotherapy, I add topical tazarotene 0.1% gel (or topical tretinoin²³) and/or 5-fluorouracil cream daily and continue cryotherapy. Warts sometimes respond to these combinations, but it is unclear whether the effectiveness of combination therapy results from the topical treatment or the additional cryotherapy. Some clinicians use oral isotretinoin for recalcitrant warts. However, this off-label treatment has numerous side effects, is expensive, and requires special prescription documentation.

Some experts recommend imiquimod for treating recalcitrant subungual and periungual warts²⁴ and plantar warts.²⁵ The patient applies the cream after he or she has removed the top of the wart with salicylic acid overnight under occlusion. I have not found imiquimod to be effective for hand and foot warts, but I have used it successfully for flat warts on the shins and arms that have resisted salicylic acid and cryotherapy.

Some studies have found imiquimod to be effective. The authors of one study involving children with recalcitrant nongenital warts noted a cure rate of 88.9% with twice-daily applications of imiquimod.²⁶ Treatment lasted for 2 to 12 months, with a mean duration of 5.8 months. Another small study demonstrated similar results.²⁷ Imiquimod was applied once a day and occluded for a total of 4 weeks; of the 10 study participants, 9 had complete clearance of recalcitrant common warts. Because these studies were uncontrolled and because imiquimod is expensive, it is generally not recommended for the treatment of common warts.

I have used bleomycin to treat warts, especially plantar warts, with success.²⁸ I use a bifurcated needle to introduce bleomycin, 0.5 to 1 U/mL of normal saline, into each wart. This treatment is best reserved for patients with recalcitrant warts because of such possible adverse effects as pain during and after treatment, pigment changes, transient or persistent Raynaud phenomenon, necrotic eschar, scarring, and nail damage.²⁹ Bleomycin is listed as FDA Pregnancy Category D.

Intralesional immunotherapy. Experts believe that the delayed-type hypersensitivity reaction induced by these antigens increases the ability of the immune system to recognize and clear HPV. Candida skin test antigen is generally used.^1,30 I inject 0.1 mL of antigen into the largest wart, wait several weeks, then inject 0.1 to 0.2 mL into additional warts. I have had substantial success with the 1 in 13 patients with treatment-resistant warts in whom I have used it. I intend to continue using this technique, but it is not likely to be a definitive treatment for warts.

However, in one study of the use of intralesional mumps or Candida antigens in 47 children, warts completely resolved in 47% of participants and 75% to 99% resolution occurred in 13% of participants.³¹ In 34% of participants, complete clearance of all warts distant from the injection site occurred. The most common side effects of Candida antigens are itching at the injection site and a flu-like illness that lasts less than 24 hours and is relieved by NSAIDs.

Some practitioners use oral cimetidine³² (400 mg tid) or oral zinc sulfate (10 mg/kg/d, up to 600 mg/d).³³ I have found these agents to be ineffective; however, since they do not have serious side effects, I do not object if patients wish to try them. Positive outcomes have been reported with topical virucidal agents, such as formaldehyde (formalin) and glutaral (glutaraldehyde), but I have never used them.³⁴

Alternative therapies. Some reports demonstrate the effectiveness of positive suggestion, treatment simulations,³⁵ and hypnosis.³⁶ However, patients whom I have referred to psychiatrists for these treatments have reported no success. (Of course, if these therapies worked, patients would not return to me for further treatment.)

SPECIAL TREATMENT CONSIDERATIONS

Warts in children. Children younger than 12 years do not tolerate the pain of cryotherapy very well. A better choice is one of the salicylic acid-podophyllin-cantharidin combinations; these achieved a cure rate of 81% in one study.^37,38 I also have used oral cimetidine at a dose of 20 mg/ kg/d without much success and liquid nitrogen on a cotton wool bud.

Filiform warts. Filiform verrucae, which typically present in adults, are most common on the face and neck and may be easily snipped off at the base with an iris or Gradle scissors. Local anesthesia is sometimes required.³⁹

Recalcitrant warts. Periungual and subungual warts are the warts least likely to clear with treatment.⁴⁰ Some authorities remove the nail and treat such warts; however, many patients object to this procedure. About 10% to 20% of my patients improve with this therapy, but multiple treatments are required.

Another type of recalcitrant wart is found in patients with compromised immune systems, such as transplant patients who are taking immunosuppressive medications and those with HIV infection. This phenomenon underscores the need to support the immune system in the treatment of warts. Oral retinoids are an option for warts in transplant patients. Although they reduce the incidence of squamous cell cancer, their long-term use requires monitoring and may be associated with adverse effects.

References:

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