Cutaneous warts (common, plantar, and flat warts)

INTRODUCTION — Human papillomaviruses (HPVs) infect epithelial tissues of skin and mucous membranes. The most common clinical manifestations of HPV infection are warts (verrucae). There are over 200 distinct HPV subtypes; some tend to infect specific body sites. HPV type 1 commonly infects the soles of the feet and produces plantar warts, while HPV types 6 and 11 infect the anogenital area and cause anogenital warts. (See "Condylomata acuminata (anogenital warts) in adults: Epidemiology, pathogenesis, clinical features, and diagnosis".)

The clinical findings and management of cutaneous warts (including common, plantar, and flat warts) will be reviewed here. Anogenital warts (condylomata acuminata) are reviewed separately. (See "Condylomata acuminata (anogenital warts) in children" and "Condylomata acuminata (anogenital warts) in adults: Epidemiology, pathogenesis, clinical features, and diagnosis" and "Condylomata acuminata (anogenital warts): Management of external condylomata acuminata in adult males" and "Condylomata acuminata (anogenital warts): Treatment of vulvar and vaginal warts".)

EPIDEMIOLOGY AND TRANSMISSION — Cutaneous warts occur most commonly in children and young adults and are more common among certain occupations, such as handlers of meat, poultry, and fish [1]. Predisposing conditions for extensive or recalcitrant involvement include atopic dermatitis and conditions associated with decreased cell-mediated immunity (eg, acquired immunodeficiency syndrome [AIDS], organ transplantation) [2,3].

Infection with human papillomavirus (HPV) occurs by direct skin contact, with maceration or sites of trauma predisposing patients to inoculation. Latent HPV infection also may occur in normal skin. The reservoir for HPV appears to be individuals with clinical or subclinical infection. Transmission via inanimate objects has been proposed but has not been proven. The incubation period is approximately two to six months.

Spontaneous remission of warts occurs in two-thirds of children within two years; spontaneous resolution in adults tends to be slower and may take up to several years or longer [4]. Warts in patients with intact cellular immunity are the most likely to regress without therapy [5,6]. Recurrence is common.

CLINICAL FEATURES — Cutaneous warts may manifest as common warts (verruca vulgaris), plantar warts (verruca plantaris), and flat (plane) warts (verruca plana) (picture 1A-H).

Cutaneous warts are also described based upon location (eg, periungual warts) or morphology (eg, filiform or mosaic warts). Warts may occur singly, in groups, or as coalescing warts forming plaques. Mosaic warts are coalescing plantar warts.

DIAGNOSIS — The diagnosis of cutaneous warts is based upon clinical appearance. Paring of overlying hyperkeratotic debris on plantar or common warts usually reveals thrombosed capillaries, a feature that can help with diagnosis (picture 1G). If dermoscopy is performed, the thrombosed capillaries may appear as homogenous black to red dots and globules [7,8].

Palmar and plantar warts classically obscure normal skin markings, also known as dermatoglyphics (picture 1G). Rarely, a biopsy is indicated to confirm the diagnosis. (See "Skin biopsy techniques", section on 'Shave biopsy'.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of verrucae includes the following:

●Corn – A corn (also known as clavus) may obscure normal skin lines but lacks thrombosed capillaries (picture 2A-B). (See "Overview of benign lesions of the skin", section on 'Calluses and corns'.)

●Black heel (talon noir) – Dried erythrocytes deposited in the epidermis of the heel after trauma can mimic thrombosed capillaries within plantar warts (picture 3A-B). Unlike warts, the dark color can be removed by superficial paring and skin lines are not disrupted.

●Seborrheic keratosis – Seborrheic keratoses are papules or plaques with a "stuck-on" appearance and horn cysts visible on close examination (picture 4). They are often pigmented. Dermoscopy can be useful for diagnosis. (See "Overview of benign lesions of the skin", section on 'Seborrheic keratosis'.)

●Acrochordon – Acrochordons, or skin tags, are pedunculated skin-colored papules (picture 5). Filiform warts may be pedunculated but have finger-like keratotic projections (picture 1H). (See "Overview of benign lesions of the skin", section on 'Acrochordon (skin tag)'.)

●Lichen planus and lichen nitidus – The flat-topped papules of lichen planus and globoid papules of lichen nitidus may be confused with flat warts (picture 6A-C). A symmetric distribution, Wickham's striae, and oral involvement suggest lichen planus. Lichen nitidus typically presents as numerous 1 to 2 mm smooth papules that have a rounder appearance than flat warts. (See "Lichen planus".)

●Malignancy – Cutaneous malignancies, such as squamous cell carcinoma and amelanotic melanoma, should be considered when wart-like papules or plaques have irregular growth, ulceration, and/or resist therapy (picture 7A-B). (See "Cutaneous squamous cell carcinoma (cSCC): Clinical features and diagnosis" and "Melanoma: Clinical features and diagnosis".)

MANAGEMENT — Treatment of cutaneous warts may not be necessary. Spontaneous resolution may occur, particularly in children. (See 'Epidemiology and transmission' above.)

Common reasons for treatment include:

●Associated pain, discomfort, or functional impairment

●Patient concern for cosmesis or social stigma

●Persistent wart(s)

●Immunosuppression (a risk factor for extensive, resistant warts)

A variety of therapeutic interventions are available. Common approaches include chemical or physical destruction of affected tissue (eg, salicylic acid, cryotherapy, cantharidin, trichloroacetic acid, surgery, laser), enhancement of the local immune response (eg, imiquimod, topical or intralesional immunotherapy), and antiproliferative therapy (eg, topical fluorouracil, bleomycin) [4].

High-quality studies of therapeutic interventions are limited, complicating definitive recommendations on the best approach to treatment [9]. In general, the approach is dependent upon the type of wart (ie, common, plantar, flat, or filiform) and influenced by wart location, treatment side effects, clinician skill, and patient preference. For children, the ability to tolerate discomfort impacts treatment selection. (See 'Common warts and plantar warts' below and 'Flat warts' below and 'Filiform warts' below.)

The endpoint of treatment is the absence of visible warts. On the soles of the feet or palms, the reappearance of normal dermatoglyphics (skin lines) supports resolution. However, clinical resolution does not confirm eradication of the virus.

Patient education — The option to defer treatment should be discussed with patients or their guardians. Although most warts in immunocompetent patients eventually resolve without treatment, warts may spread or persist and resolution is unpredictable.

Many wart therapies require prolonged treatment or multiple office visits and have inconsistent efficacy. Clinicians should communicate expectations for the treatment course as well as the possibility of treatment failure and recurrence.

Common warts and plantar warts — The approach to the treatment is similar for common warts (verruca vulgaris) and plantar warts (verruca plantaris).

First-line treatment — Topical salicylic acid and cryotherapy with liquid nitrogen are the most common treatments for common and plantar warts and have the strongest evidence for efficacy [4]. Plantar warts may be less likely to respond than common warts [10].

Salicylic acid — Topical salicylic acid exfoliates the affected epidermis and may also stimulate local immunity [4]. Advantages of salicylic acid include self-administration, painless application, and minimal risk for serious side effects:

●Efficacy – A 2012 meta-analysis of randomized trials found salicylic acid superior to placebo for clearance of warts (relative risk [RR] 1.56, 95% CI 1.20-2.03) [9]. Reports of the likelihood of wart clearance following salicylic acid therapy range from 0 to more than 80 percent [9].

●Administration – Products containing salicylic acid in concentrations between 17 and 50% are typically used for treatment. The higher 40 to 50% concentrations are usually reserved for application to sites with a thick stratum corneum, such as the palms or soles. Salicylic acid is available in liquid, ointment, pad, and patch forms. In the United States, concentrations above 40% are available as compounded products.

Salicylic acid is applied directly to the wart. Skin should be dry prior to application. Application is typically repeated daily. Duct tape or other tape is useful for securely attaching salicylic acid pads and occluding salicylic acid ointment on the skin. If tape is used, the tape and salicylic acid can be replaced every 48 hours. Salicylic acid treatment should not extend beyond 12 weeks without assessment by a clinician.

Paring of the wart should be repeated periodically to minimize build-up of hyperkeratotic debris. Soaking the wart for five minutes can facilitate paring and removal of hyperkeratotic debris.

Salicylic acid is often combined with other wart treatments in an attempt to improve the response. We often combine salicylic acid therapy with cryotherapy, with salicylic acid applied between cryotherapy treatments. Data to confirm benefit are limited. A meta-analysis of two randomized trials found greater benefit of combination therapy with a topical salicylic acid/lactic acid product and cryotherapy compared with topical treatment alone for hand warts but not foot warts [9]. (See 'Cryotherapy' below.)

●Side effects – Local skin irritation is a common and expected side effect. If significant, the frequency of application should be reduced. Salicylic acid should not be used in patients with peripheral neuropathy due to a reduced ability to detect tissue damage and increased risk for poor healing.

Cryotherapy — Cryotherapy with liquid nitrogen is a common clinician-administered treatment. A disadvantage of cryotherapy is the pain associated with treatment. As a result, cryotherapy is primarily used for warts in older children and adults and often avoided in young children:

●Efficacy – Cure rates from cryotherapy in randomized trials range from 14 to more than 90 percent [9]. Although a statistically significant benefit of liquid nitrogen cryotherapy over placebo was not detected in a 2012 meta-analysis of randomized trials (RR 1.45, 95% CI 0.65-3.23), the meta-analysis did not find a significant difference in efficacy between cryotherapy and salicylic acid, which appeared to be more effective than placebo [9] (see 'Salicylic acid' above). A randomized trial that compared cryotherapy (applied via cotton bud every two weeks until wart resolution) with salicylic acid 40% ointment (applied daily under tape occlusion until wart resolution) and no treatment for common warts found cryotherapy more effective than salicylic acid and no treatment [10].

●Administration – Plantar warts and other hyperkeratotic warts should be pared before treatment. Liquid nitrogen can be administered with a cryospray or a cotton bud dipped in liquid nitrogen. Wart virus can survive in liquid nitrogen; therefore, dispensing a small aliquot of liquid nitrogen into a disposable cup is recommended rather than dipping cotton buds into a communal flask [11]. The goal is to create a visibly frozen area that includes the wart and approximately 2 mm of the surrounding normal skin and disappears within 30 to 60 seconds after application. Two freeze-thaw cycles may lead to improved resolution of thick or plantar warts [12].

Treatment is repeated every two to three weeks until wart resolution. If a response does not occur within six treatments, it is reasonable to transition to an alternative treatment [4].

Cryotherapy should be applied cautiously on the digits to prevent severe pain and possible neuropathy. Periungual warts should be treated with caution due to avoid damage to the nail matrix and permanent nail dystrophy.

Cryotherapy is often combined with salicylic acid treatment in an attempt to augment efficacy. However, greater benefit of this combination compared with cryotherapy alone is not proven [9]. (See 'Salicylic acid' above.)

●Side effects – The acute response to cryotherapy ranges from minimal erythema to hemorrhagic blistering, pain, and tenderness. Healing usually occurs within four to seven days. Local hypopigmentation can occur, and patients with dark skin should be treated with caution. Occasionally, blistering can result in spread of the virus to adjacent skin, resulting in a larger wart.

Refractory warts — The best approach to treatment-refractory warts is unclear. Therapies such as topical immunotherapy with contact allergens, intralesional bleomycin, and topical fluorouracil may be beneficial.

Topical immunotherapy with contact allergens — Limited data suggest that contact allergens, such as squaric acid dibutylester (SADBE), dinitrochlorobenzene (DNCB), and diphenylcyclopropenone (DPCP), can be effective treatments. An advantage of topical immunotherapy is the ease of treating multiple warts simultaneously.

Topical immunotherapy should be performed by clinicians with experience in this procedure. Treatment is usually administered by a dermatologist:

●Efficacy – DNCB has been evaluated in randomized trials. A meta-analysis of two small randomized trials with a total of 80 patients suggested that DNCB is more effective than placebo (RR 2.12, 95% CI 1.38-3.26) [9].

The efficacy of SADBE is supported by an uncontrolled study of 568 adults and children with multiple and resistant warts in which sensitization with 3% SADBE was followed by twice-weekly clinician applications of serial dilutions of SADBE (0.03 to 3%) for up to 10 weeks [13]. Of the 443 patients who completed the study, 382 had complete resolution of warts (86 percent). The average time to resolution of periungual or subungual warts, flat warts, and multiple common warts were 10, 8, and 6 weeks, respectively.

There are multiple reports of successful treatment with DPCP, many involving warts refractory to other therapies [14-24]. An uncontrolled prospective study of 134 adolescents and adults with refractory palmoplantar or periungual warts found that among 111 patients who completed the study (treatment with DPCP once weekly for eight weeks and a follow-up period of four months), 49 (44 percent) achieved a complete response and 18 (16 percent) had partial improvement by the end of follow-up [20]. Two retrospective studies have reported higher rates of clearance among patients who have complied with treatment [16,18].

In addition, successful treatment with DPCP has been reported in immunosuppressed patients [25]. However, treatment may be less likely to be effective in this population than in immunocompetent patients [25].

●Administration – Concern for the mutagenic potential of DNCB has led to the infrequent use of this agent [26,27]. SADBE and DPCP are typically purchased from a chemical distributor, and the solutions for application are subsequently prepared by a pharmacist or the clinician.

Similar to the use of these agents for alopecia areata, treatment begins with sensitization of the patient to the contact allergen by application of the sensitizer to a small unaffected area (eg, 4 x 4 cm area on the medial upper arm). Approximately two weeks after sensitization, the clinician begins a series of applications of the contact allergen to the wart with a lower concentration of the agent. The concentration is subsequently titrated upward to obtain and maintain a mild contact dermatitis in the treatment area. (See "Alopecia areata: Management", section on 'Topical immunotherapy'.)

Regimens used for SADBE have varied widely [13,26,28-30]. Sensitization is typically performed with a 1 to 3% concentration of SADBE, and treatment is usually begun with concentrations of 0.01% or higher. The frequency of clinician application of SADBE ranges from every few days to every few weeks. Based upon a separate retrospective study of 61 children with warts, a treatment regimen in which SADBE is applied more frequently by patients (or caregivers) at home may be an effective and safe alternative to clinician-administered treatment [26].

For DPCP, sensitization is often performed with 1 to 3% DPCP. This is followed by applications of DPCP to the warts every one to three weeks with initial concentrations in the range of 0.001 to 3%.

●Side effects – Erythema, itching, dyspigmentation, blistering, and local or diffuse eczematous eruptions are potential side effects of topical immunotherapy with contact allergens [31]. Treatment of warts with DPCP has also been linked to the development of urticaria [32-34].

Intralesional bleomycin — Bleomycin is a chemotherapeutic agent most often used for the treatment of malignancies that may be effective for warts through cytotoxic or antiviral effects [9]. A disadvantage of intralesional bleomycin is both immediate and persistent pain associated with injection:

●Efficacy – The use of bleomycin for cutaneous warts has been evaluated in several placebo-controlled randomized trials with cure rates between 16 and 94 percent of warts and disparate conclusions on efficacy [9]. Whereas some trials found efficacy of intralesional bleomycin, others found no benefit [9]. In two randomized trials, bleomycin was more effective than cryotherapy [35,36].

●Administration – Bleomycin is either injected directly into warts or applied to the surface of the wart followed by pricking the surface of the wart multiple times to allow for penetration of the drug (so-called "scarification" technique) [4,37]. Often, bleomycin is given as a 1 mg/mL solution, although lower-strength preparations (0.5 mg/mL or 0.1 mg/mL) also may be effective [4,38]. Bleomycin treatment induces significant pain, and prior or simultaneous injection of local anesthesia is recommended.

●Side effects – Pain from bleomycin injection typically lasts for one to two days and is followed by tissue necrosis with the formation of a black eschar. Treatment with bleomycin is not recommended for children, pregnant women, immunosuppressed patients, or patients with vascular disease because of systemic absorption [37]. Dyspigmentation may occur at the site of treatment.

Fluorouracil — Topical or intralesional fluorouracil (FU) may be a useful treatment. Efficacy may result from antineoplastic and antimetabolite effects that inhibit DNA and RNA synthesis and wart proliferation [9]:

●Efficacy – Several randomized trials have demonstrated benefit of topical FU for cutaneous warts, with cure rates around 50 percent [9]. Randomized trials also support benefit of intralesional FU. One single-blind randomized trial in which paired periungual or plantar warts (n = 315) in each of 76 patients were randomly assigned to receive either an injection containing FU, lidocaine, and epinephrine or a saline injection once weekly for up to four weeks found that 70 percent of warts treated with FU completely responded, compared with 29 percent in the placebo group [39]. A smaller double-blind trial of 40 patients in which paired common warts were randomly assigned to similar treatment regimens found complete response rates in FU and placebo-treated warts of 65 and 35 percent, respectively [40].

●Administration – Topical FU is often applied daily under occlusion for 4 to 12 weeks. Intralesional injections are administered into the dermis. In the randomized trials, patients were given a series of four once-weekly injections from a solution containing 4 mL of FU (50 mg/mL) combined with 1 mL of a mixture of lidocaine (20 mg/mL) and epinephrine (0.0125 mg/mL). The amount injected should be sufficient to infiltrate the area under the wart.

●Side effects – Administration of FU may result in erythema, edema, hyperpigmentation, hypopigmentation, ulceration, necrosis, onycholysis, or scarring [39-41]. Pain and burning sensations may occur at the time of injection [39].

Other treatments — A variety of additional treatments are used for warts. These interventions have limited or conflicting evidence for efficacy and are often used in conjunction with wart paring and topical salicylic acid.

Cantharidin — Cantharidin 0.7% (also referred to as "beetle juice") is a clinician-administered blistering agent commonly used for molluscum contagiosum and occasionally used for warts. Advantages of cantharidin are painless application and the ease of treating multiple warts.

Cantharidin is applied to individual warts and then covered with tape. Blistering will occur within 2 to 24 hours, after which time the tape should be removed and the medication washed off with soap and water. Blistering can be uncomfortable; some patients experience local swelling and significant pain. Recurrence at the periphery of the treated site, forming a "doughnut wart," is a risk of this treatment.

Cantharidin can be reapplied every three weeks [4]. If a response is not evident within four treatments, it is appropriate to change to a different treatment.

Imiquimod — Imiquimod is a topical immunomodulator that induces local cytokine induction, is effective, and is US Food and Drug Administration (FDA)-approved for the treatment of anogenital warts. Although uncontrolled studies and a right-left comparison study have reported benefit of imiquimod 5% cream for nonanogenital cutaneous warts with widely varying rates of clearance [42-47], randomized trial data to support efficacy are limited [9]. A randomized trial in which imiquimod 5% cream (plus salicylic acid 15% solution as a keratolytic for warts located on palms or soles) applied five days per week was compared with cryotherapy administered every two weeks found that clearance of cutaneous warts occurred in 30 of 37 children (81 percent) treated with imiquimod and 33 of 49 children (67 percent) treated with cryotherapy after three months [48]. The difference in effect was not statistically significant except for among the subgroup of plantar warts, which exhibited a better response to imiquimod and salicylic acid treatment.

Imiquimod is nonscarring and painless to apply. The optimal regimen is unclear. Reported regimens vary from application several days per week to twice daily, with or without occlusion. In our practices, we often instruct patients to apply imiquimod 5% cream and salicylic acid on alternate nights and to wash imiquimod off the skin in the morning. Warts should be pared prior to application. Three months of treatment are usually recommended before considering alternative therapies.

Local inflammatory skin reactions are common and can be significant, and there are rare reports of systemic side effects. The frequency of application can be reduced if serious skin reactions occur.

Trichloroacetic acid — Trichloroacetic acid (TCA) has been used for warts on the palms and soles. A single-blind randomized trial that compared once-weekly application of 80% TCA solution with once-weekly application of 35% TCA solution in 62 patients with common warts found better results with the 80% solution (47 versus 12 percent of patients who completed the study achieved clearance of more than 75 percent of warts) [49,50].

A 50 to 80% solution of TCA is applied to pared warts with a wooden toothpick every 7 to 10 days for up to eight weeks. Burning or stinging sensations may occur at the site of application.

Duct tape — There is conflicting evidence about the effectiveness of occlusion with duct tape. Although one trial in children found superiority of treatment with standard duct tape to cryotherapy [51], a meta-analysis of two placebo-controlled randomized trials [52,53] failed to find a statistically significant difference between the efficacy of clear duct tape and placebo (RR 1.43, 95% CI 0.51-4.05) [9]. Descriptions of these three trials are provided below [51-53]:

●A study of 61 children and adolescents (ages 3 to 22) concluded that covering warts with duct tape was more effective than cryotherapy [51]. Treatment involved keeping the wart covered with duct tape for cycles lasting six days and then removing the tape, soaking the wart, debriding the wart with an emery board or pumice stone, and then leaving the wart uncovered on the sixth night; the duct tape was reapplied the next morning. Treatment was continued until wart resolution or for a maximum of two months.

Resolution rates were significantly higher with duct tape than with cryotherapy (85 versus 60 percent). The majority of warts that resolved with duct tape did so within 28 days of treatment; warts were unlikely to resolve if no response was seen within two weeks. There were nine patients lost to follow-up, and blinding of evaluators was limited. The study included patients with warts in various locations, including finger and plantar warts, but excluded periungual warts because of concerns about nail dystrophy in the cryotherapy arm of the study.

●In contrast, a somewhat more rigorous study in 103 children (ages 4 to 12) found no statistically significant benefits with duct tape [52]. Patients were treated with either a clear brand of duct tape according to the protocol above or with a corn pad (a ring of material surrounding the wart, intended as a placebo) one night per week; both groups also performed soaking and debridement one night per week as per the protocol above. The evaluator was blinded to treatment for most patients, and no patients were lost to follow-up. After six weeks, rates of wart resolution were similar in the duct tape and corn pad groups (16 versus 6 percent, p = 0.12) and much lower than the rates seen in the earlier trial.

●A similar trial comparing a clear brand of duct tape with a control treatment with a moleskin pad in 90 adults also found no difference in the rate of wart resolution at the end of two months (21 versus 22 percent) [53].

Participants in the latter two trials that used clear duct tape apparently found the duct tape to be much more difficult to keep applied. The researchers in the adult trial were initially informed by the manufacturer that the clear duct tape had the same adhesive as their standard silver duct tape; however, they later learned that silver duct tape from that manufacturer uses a rubber-based adhesive and clear duct tape an acrylic-based adhesive [53]. The trial that used clear duct tape in children also used duct tape made by the same manufacturer [52].

It is possible that the decreased stickiness of clear duct tape directly reduced efficacy or that the type of adhesive is related to the efficacy of duct tape. Alternatively, the less rigorous design of the earlier trial could have led to a false conclusion of benefit.

In summary, it remains uncertain whether duct tape is effective. In patients who are treated with duct tape, it would make sense to choose a silver brand that is adequately sticky to remain on the skin. In nondiabetic patients with no peripheral artery disease and no neuropathy who are free from skin erosions, duct tape can be combined with salicylic acid applied to the wart itself and not the surrounding skin. (See 'Salicylic acid' above.)

Pulsed dye laser — Pulsed dye lasers may treat warts by targeting hemoglobin, resulting in the destruction of wart vasculature [54,55]. Randomized trial data are limited to a trial in which 40 patients with common or plantar warts were randomly assigned to treatment with a pulsed dye laser or to "conventional treatment" with cryotherapy or cantharidin [54]. The trial did not find a significant difference in efficacy between the two groups. Among the 35 patients with a total of 194 warts who completed the study, complete responses occurred in 66 percent of warts in the pulsed dye laser group and 70 percent of warts in the "conventional treatment" group.

One of the largest studies evaluating pulsed dye laser therapy, a retrospective study of 227 patients treated for recalcitrant common or plantar warts, found favorable results [56]. After an average of six treatments with higher fluence levels than typically used in other studies (12.5 to 15 J/cm²), 86 percent of the 209 patients who were not lost to follow-up achieved complete or almost complete resolution of warts. Treatment intervals of four weeks or less (eg, every three to four weeks) were associated with higher success rates than longer treatment intervals.

Warts should be pared prior to pulsed dye laser treatment. A series of treatments is usually required. A short course of salicylic acid therapy prior to laser therapy may reduce the number of treatment sessions required for resolution [57]. Potential side effects include pain, blistering, dyspigmentation, and scarring.

Intralesional immunotherapy — Intralesional immunotherapy with skin test antigens (ie, mumps, Candida, or Trichophyton antigens) may lead to the resolution both of the injected wart and additional untreated warts [58,59]. A single-blind trial in 201 patients with warts who demonstrated at least a 5 mm response to skin testing with at least one of the above antigens randomly assigned patients to receive one of four treatments injected into a single wart: 0.3 mL of an antigen that produced a skin test response, antigen plus interferon alfa-2b, interferon alone, or saline [60]. Patients received the injection every three weeks until the wart was completely cleared or for a maximum of five injections. Patients treated with skin test antigens had significantly greater resolution of the injected wart than those treated with interferon alone or saline (60 versus 26 and 22 percent, respectively). Additionally, more patients with multiple warts experienced complete resolution of at least one wart other than the injected wart (49 versus 9 and 19 percent).

Although the results of this study appear to show benefit, it used an unblinded assessment of outcome, performed an unplanned interim analysis that led to stopping the trial because of a lack of availability of mumps antigen, and changed the protocol of two arms of the trial to replace granulocyte-macrophage colony-stimulating factor (GM-CSF) injection with interferon injection because of severe side effects with GM-CSF. Additionally, there appeared to be an increased rate of fever and myalgias in patients treated with immunotherapy, particularly in the group treated with both antigen and interferon.

When performing intralesional immunotherapy, we typically use Candida antigen and inject 0.3 mL intradermally and as superficially as possible into the largest wart. Injection can be repeated every four weeks.

Surgery — Surgical removal (eg, shave removal or curettage with or without electrodessication) is a treatment option for common warts. An advantage of surgery is the immediate removal of the wart. However, scarring often limits use in cosmetically sensitive areas. Surgery on the sole of the foot is often avoided due to risk for permanently painful scars.

Oral cimetidine — Cimetidine, an H2 receptor antagonist, has been used to treat recalcitrant warts based upon the theory that H2 receptors are present on T-suppressor cells, and blocking the receptors may therefore result in an increase in cell-mediated immunity. Although uncontrolled studies suggested that cimetidine therapy (30 to 50 mg/kg per day in four divided doses for up to three months) may be effective [61,62], randomized trials have not found superiority over placebo [63-65].

Other — Other therapies reported effective include topical 1 to 3% cidofovir [66], formaldehyde 0.5 to 3% solution [67], glutaraldehyde 10 to 20% solution or gel [68], intralesional cidofovir [69,70], intradermal Bacillus Calmette-Guérin vaccine [71], oral acitretin [72], oral zinc sulfate [73], carbon dioxide laser therapy [74], thermotherapy [75,76], photodynamic therapy [77], and topical viable Bacillus Calmette-Guérin [78].

The use of human papillomavirus (HPV) vaccination to treat recalcitrant warts is being increasingly reported [79-82]. In a retrospective study of 30 patients treated with the quadrivalent HPV vaccine for multiple warts, 14 (47 percent) had complete remission, 5 (17 percent) had a partial response, and 11 (37 percent) had no response [82]. There were no statistically significant differences in demographics or duration, site, or number of warts between responders and nonresponders, and there were no severe adverse events. In a separate retrospective study of 16 adults who received the quadrivalent HPV vaccine for recalcitrant warts, 44 percent achieved complete clearance, 38 percent had persistent or new warts, and 19 percent were lost to follow-up [83].

Resolution of cutaneous warts after administration of the quadrivalent HPV vaccine in young adults and children has been documented [79-82]; however, the efficacy of this intervention remains to be proven. (See "Human papillomavirus vaccination", section on 'Available vaccines'.)

Botanical products have been proposed for the treatment of warts, but evidence to support use is scant.

Flat warts — Many treatments for common and plantar warts also may be effective for flat warts. However, the efficacy of most interventions for flat warts has not been evaluated in randomized trials, and data are insufficient for conclusions on comparative efficacy.

Cryotherapy and topical medications such as salicylic acid, topical tretinoin [84], imiquimod [85-87], and FU [88] are among the most common treatments. The mechanisms of action of cryotherapy, salicylic acid, imiquimod, and FU are likely similar to their mechanisms for common and plantar warts; the efficacy of topical tretinoin may involve the induction of a local irritant reaction.

Cryotherapy sessions are often repeated every three to four weeks as needed. Topical tretinoin, imiquimod, and FU are usually applied on a daily basis, with a response expected within several weeks.

The side effects of treatments should be carefully considered prior to treatment selection, particularly for flat warts on cosmetically sensitive areas such as the face. Although salicylic acid and cryotherapy are well-accepted first-line treatments for nonfacial flat warts, salicylic acid is usually avoided for facial flat warts because of the absence of significant hyperkeratosis and the potential for excessive skin irritation. Similarly, cryotherapy is often avoided for facial flat warts because of risk for hypopigmentation. In our practices, we typically use tretinoin, imiquimod, or FU as first-line treatments for flat warts on the face. Of note, these topical treatments may cause skin irritation resulting in postinflammatory hyperpigmentation. Patients with dark skin are at greatest risk for postinflammatory hyperpigmentation.

Less common treatments reported effective in small numbers of patients include glycolic acid 15% plus salicylic acid 2% [89], cantharidin [90], topical potassium hydroxide [91], topical Bacillus Calmette-Guérin [78], topical zinc sulfate [92], oral propolis [93], topical contact immunotherapy [19,94,95], intralesional immunotherapy with Candida antigen [96], photodynamic therapy [97-99], pulsed dye laser [55,100], frequency-doubled Q-switched neodymium-doped yttrium aluminium garnet (Nd:YAG) laser [101], and acupuncture [102].

Oral isotretinoin has been evaluated for flat warts [103,104]. Isotretinoin (30 mg per day) was more beneficial than placebo in a randomized trial of 29 patients with recalcitrant facial flat warts [103]. The side effect profile of oral isotretinoin makes it a less favorable first-line treatment.

Filiform warts — Given the small size and pedunculated morphology of filiform warts, the most common treatments are surgical removal and cryotherapy. Surgical removal of filiform warts can be performed with a "snip excision" using surgical scissors or shave removal. Electrodessication or topical aluminum chloride is useful for hemostasis.

Cryotherapy is often performed with a contact freezing technique to limit damage to the surrounding skin. Surgical forceps, a needle holder, or a hemostat are briefly dipped in liquid nitrogen and used to grasp and freeze the wart. Alternatively, cryotherapy can be performed with a cryospray or cotton bud techniques.

PREVENTION — Since warts are infectious, patients should avoid deliberately manipulating warts on themselves or others. Using slippers or other footwear in public showers also may reduce the chance of transmission [105].

In addition, tools used for paring down warts (eg, nail file, pumice stone, etc) should not be reused on normal skin or nails and should not be shared with others. Hair-bearing skin with warts should be shaved with electric razors or not at all.

Human papillomavirus (HPV) vaccines are available for the prevention of genital warts and HPV-related anogenital cancers. Given the challenges associated with treating cutaneous warts, the development of highly effective vaccines for the prevention of nonanogenital warts would be valuable. (See "Human papillomavirus vaccination".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cutaneous warts".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Skin warts (The Basics)")

●Beyond the Basics topics (see "Patient education: Common warts, plantar warts, and flat warts (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Epidemiology and transmission – Cutaneous warts are a common skin infection caused by human papillomavirus (HPV) that most often occurs in children and young adults. Medical conditions such as atopic dermatitis and immunosuppression may increase risk for infection. Warts are usually transmitted via skin-to-skin contact. (See 'Epidemiology and transmission' above.)

●Clinical features – Major types of cutaneous warts include common warts (verruca vulgaris), plantar warts (verruca plantaris), and flat (plane) warts (verruca plana) (picture 1A-H). Additional terms used to further describe specific presentations are periungual warts, filiform warts, and mosaic warts. (See 'Clinical features' above.)

●Decision to treat – Many warts eventually spontaneously resolve; therefore, treatment is not always necessary. Common reasons for treatment include:

•Associated pain, discomfort, or functional impairment

•Patient concern for cosmesis or anxiety related to perceived social stigma

•Persistent wart(s)

•Immunosuppression (see 'Management' above)

●Treatment of common or plantar warts – For patients with common or plantar warts, we suggest topical salicylic acid as first-line treatment (Grade 2A). Cryotherapy is an alternative first-line treatment; however, tolerance for associated pain and other side effects (eg, hypopigmentation) limits use in some patients. (See 'First-line treatment' above.)

The best approach to patients with refractory cutaneous warts is unclear. Topical immunotherapy with contact allergens, intralesional bleomycin, or topical or intralesional fluorouracil may be useful for such patients. (See 'Refractory warts' above.)

●Treatment of flat warts – Flat warts are usually treated with cryotherapy or topical agents such as tretinoin, imiquimod, or fluorouracil. Filiform warts are easily treated with cryotherapy or surgery. (See 'Flat warts' above and 'Filiform warts' above.)