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Warts
Mercedes E. Gonzalez, MD, FAAD
Herbert P. Goodheart, MD
image BASICS
  • Warts (verrucae) are benign growths that are confined to the epidermis. All warts are caused by the human papillomavirus (HPV). Warts can appear on any area of the skin or mucous membranes. Common warts are predominantly seen in children and young adults.
  • Clinically, warts are rather arbitrarily described as the following:
    • Common warts (verrucae vulgaris)
    • Plantar warts (verrucae plantaris)
    • Flat warts (verrucae plana)
    • Venereal warts (condyloma acuminatum)
    • Epidermodysplasia verruciformis is a rare, lifelong hereditary disorder characterized by chronic infection with HPV.
  • System(s) affected: skin/exocrine
DESCRIPTION
  • Common warts are most often found at sites subject to frequent trauma, such as the hands and feet. Because warts often vary widely in shape, size, and appearance, the various descriptive names for them generally reflect their clinical appearance, location, or both.
  • For example, filiform (fingerlike) warts are threadlike, planar warts are flat, and plantar warts are located on the plantar surfaces (soles) of the feet.
  • Genital warts, or condyloma acuminata, may be large and cauliflower-like, or they may consist of small papules.
  • Warts on mucous membranes (mucosal papillomas), such as those in the mouth or vagina, tend to be white in color due to moisture retention.
EPIDEMIOLOGY
Incidence
  • Predominant age: young adults and children
  • Predominant sex: female = male
Prevalence
  • ˜ 7-10% of the U.S. population
  • Common warts appear 2 times as frequently in whites as in blacks or Asians.
ETIOLOGY AND PATHOPHYSIOLOGY
  • HPV is a double-stranded, circular, supercoiled DNA virus.
  • The virus infects epidermal keratinocytes, stimulating cell proliferation.
  • Various strains of DNA HPV: To date, >150 different subtypes have been identified.
  • Common warts: HPV types 2 and 4 (most common), followed by types 1, 3, 27, 29, and 57
  • Palmoplantar warts: HPV type 1 (most common), followed by types 2, 3, 4, 27, 29, and 57
  • Flat warts: HPV types 3, 10, and 28
  • Butcher warts: HPV type 7
  • The virus is passed primarily through skin-to-skin contact or from the recently shed virus kept intact in a moist, warm environment.
RISK FACTORS
  • HIV/AIDS and other immunosuppressive diseases (e.g., lymphomas)
  • Immunosuppressive drugs that decrease cellmediated immunity (e.g., prednisone, cyclosporine, and chemotherapeutic agents)
  • Pregnancy
  • Handling raw meat, fish, or other types of animal matter in one's occupation (e.g., butchers)
  • Previous wart infection
GENERAL PREVENTION
There is no known way to prevent warts.
image DIAGNOSIS
  • Most often made on clinical appearance
  • Skin biopsy, if necessary
PHYSICAL EXAM
  • Distribution of warts is generally asymmetric, and lesions are often clustered or may appear in a linear configuration due to scratching (autoinoculation).
  • Common wart: rough-surfaced, hyperkeratotic, papillomatous, raised, skin-colored to tan papules, 5 to 10 mm in diameter; several may coalesce into a larger cluster (mosaic wart); most frequently seen on hands, knees, and elbows; usually asymptomatic but may cause cosmetic disfigurement or tenderness
  • Filiform warts: These are long, slender, delicate, fingerlike growths, usually seen on the face around the lips, eyelids, or nares.
  • Plantar warts often have a rough surface and appear on the plantar surface of the feet in children and young adults.
    • Can be tender and painful; extensive involvement on the sole of the foot may impair ambulation, particularly when present on a weight-bearing surface.
    • Most often seen on the metatarsal area, heels, and toes in an asymmetric distribution (pressure points)
    • Pathognomonic “black dots” (thrombosed dermal capillaries); punctate bleeding becomes more evident after paring with a no. 15 blade.
    • Both common and plantar warts generally demonstrate the following clinical findings:
      • A loss of normal skin markings (dermatoglyphics) such as finger, foot, and hand prints
      • Lesions may be solitary or multiple, or they may appear in clusters (mosaic warts).
  • Flat warts: slightly elevated, flat-topped, skin-colored or tan papules, small (1 to 3 mm) in diameter
    • Commonly found on the face, arms, dorsa of hands, shins (women)
    • Sometimes exhibit a linear configuration caused by autoinoculation
    • In men, shaving spreads flat warts.
    • In women, they often occur on the shins, where leg shaving spreads lesions.
  • Epidermodysplasia verruciformis (rare): Widespread flat, reddish brown pigmented papules and plaques that present in childhood with lifelong persistence on the trunk, hands, upper and lower extremities, and face are characteristics.
DIFFERENTIAL DIAGNOSIS
  • Molluscum contagiosum
  • Seborrheic keratosis
  • Epidermal nevus
  • Acrochordon (skin tag)
  • Solar keratosis and cutaneous horn
  • Acquired digital fibrokeratoma
  • Squamous cell carcinoma (SCC)
  • Keratoacanthoma
  • Subungual SCC can easily be misdiagnosed as a subungual wart or onychomycosis.
  • Corns/calluses
    • Corns (clavi) are sometimes difficult to distinguish from plantar warts. Like calluses, corns are thickened areas of the skin and most commonly develop at sites subjected to repeated friction and pressure, such as the tops and the tips of toes and along the sides of the feet.
      • Corns are usually hard and circular, with a polished or central translucent core, like the kernel of corn from which they take their name.
      • Corns do not have “black dots,” and skin markings are retained except for the area of the central core.
DIAGNOSTIC TESTS & INTERPRETATION
Diagnosis
  • HPV cannot be cultured and lab testing is rarely necessary.
  • Definitive HPV diagnosis can be achieved by the following:
    • Electron microscopy
    • Viral DNA identification employing Southern blot hybridization is used to identify the specific HPV type present in tissue.
    • Polymerase chain reaction may be used to amplify viral DNA for testing.
Follow-Up Tests & Special Considerations
Skin biopsy if unusual presentation or if diagnosis is unclear
Test Interpretation
  • Histopathologic features of common warts include digitated epidermal hyperplasia, acanthosis, papillomatosis, compact orthokeratosis, hypergranulosis, dilated tortuous capillaries within the dermal papillae, and vertical tiers of parakeratotic cells with entrapped red blood cells above the tips of the digitations.
  • In the granular layer, HPV-infected cells may have coarse keratohyaline granules and vacuoles surrounding wrinkled-appearing nuclei. These koilocytic (vacuolated) cells are pathognomonic for warts.
image TREATMENT
  • The abundance of therapeutic modalities described below is a reflection of the fact that none of them is uniformly or even clearly effective in trials. Placebo treatment response rate is significant and quality of evidence in general is poor. Beyond topical salicylates, there is no clear evidence-based rationale for choosing one method over another (1)[A].
  • The choice of method of treatment depends on the following:
    • Age of the patient
    • Cosmetic and psychological considerations
    • Relief of symptoms
    • P.1141

    • Patient's pain threshold
    • Type of wart
    • Location of the wart
    • Experience of the physician
GENERAL MEASURES
  • There is no ideal treatment.
  • In children, most warts tend to regress spontaneously.
  • In many adults and immunocompromised patients, warts are often difficult to eradicate.
  • Painful, aggressive therapy should be avoided unless there is a need to eliminate the wart(s).
  • For surgical procedures, especially in anxious children, pretreat with anesthetic cream such as EMLA (emulsion of lidocaine and prilocaine).
MEDICATION
First Line
  • Self-administered topical therapy
    • Keratolytic (peeling) agents: The affected area(s) should be hydrated first by soaking in warm water for 5 minutes before application. Most overthe-counter agents contain salicylic acid and/or lactic acid; agents such as Duofilm, Occlusal-HP, Trans-Ver-Sal, and Mediplast.
  • Office-based
    • Cantharidin 0.7%, an extract of the blister beetle that causes epidermal necrosis and blistering
    • Combination cantharidin 1%, salicylic acid 30%, and podophyllin resin 5% in flexible collodion; applied in a thin coat, occluded 4 to 6 hours, then washed off.
Second Line
Home-based
  • Imiquimod 5% (Aldara) cream, a local inducer of interferon, is applied at home by the patient. It is approved for external genital and perianal warts and is used off-label and may be applied to warts under duct tape occlusion. It is applied at bedtime and washed off after 6 to 10 hours. Applied to flat warts without occlusion.
  • Topical retinoids (e.g., tretinoin 0.025-0.1% cream or gel) for flat warts
Office-based
  • Immunotherapy: induction of delayed type hypersensitivity with the following:
    • Diphenylcyclopropenone (DCP) (2)[B]
    • Dinitrochlorobenzene (DNCP)
    • Squaric acid dibutylester (SADBE): There is possible mutagenicity and side effects with this agent.
  • Intralesional injections
    • Mumps or Candida antigen
    • Bleomycin: Intradermal injection is expensive and usually causes severe pain.
    • Interferon-&agr;-2b
  • Oral therapy
    • Oral high-dose cimetidine: possibly works better in children
    • Acitretin (an oral retinoid)
  • Other treatments (all have all been used with varying results)
    • Dichloroacetic acid, trichloroacetic acid, podophyllin, formic acid, aminolevulinic acid in combination with blue light, 5-fluorouracil, silver nitrate, formaldehyde, levamisole, topical cidofovir (3)[B] or IV cidofovir for recalcitrant warts in the setting of HIV, and glutaraldehyde
  • The quadrivalent HPV vaccine has cleared recalcitrant, chronic oral, and cutaneous warts (4)[C].
COMPLEMENTARY & ALTERNATIVE MEDICINE
  • Duct tape: Cover wart with waterproof tape (e.g., duct tape). Leave the tape on for 6 days, and then soak, pare with emery board, and leave uncovered overnight; then reapply tape cyclically for eight cycles; 85% resolved compared with 60% efficacy with cryotherapy (5)[A].
  • Hyperthermia: safe and inexpensive approach; immerse affected area into 45°C water bath for 30 minutes 3 times per week
  • Hypnotherapy
  • Raw garlic cloves have demonstrated some antiviral activity.
  • Vaccines are currently in development.
Pregnancy Considerations
The use of some topical chemical approaches may be contraindicated during pregnancy or in women who are likely to become pregnant during the treatment period.
SURGERY/OTHER PROCEDURES
  • Cryotherapy with liquid nitrogen (LN2) may be applied with a cotton swab or with a cryotherapy gun (Cryogun). Aggressive cryotherapy may be more effective than salicylic acid (6)[A], but it is associated with increased adverse effects (blistering and scarring):
    • Best for warts on hands; also during pregnancy and breastfeeding
    • Fast; can treat many lesions per visit
    • Painful; not tolerated well by young children
    • Freezing periungual warts may result in nail deformation.
    • In darkly pigmented skin, treatment can result in hypo- or hyperpigmentation.
  • Light electrocautery with or without curettage
    • Best for warts on the knees, elbows, and dorsa of hands
    • Also good for filiform warts
    • Tolerable in most adults
    • Requires local anesthesia
    • May cause scarring
  • Photodynamic therapy: Topical 5-aminolevulinic acid is applied to warts followed by photoactivation (7)[B].
  • CO2 or pulse-dye laser ablation: expensive and requires local anesthesia
  • For filiform warts: Dip hemostat into LN2 for
10 seconds, then gently grasp the wart for
10 seconds and repeat. Wart sheds in 7 to 10 days.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
1/3 of the warts of epidermodysplasia may become malignant.
PROGNOSIS
  • More often than not (especially in children), warts tend to “cure” themselves over time.
  • In many adults and immunocompromised patients, warts often prove difficult to eradicate.
  • Rarely, certain types of lesions may transform into carcinomas.
REFERENCES
1. Kwok CS, Gibbs S, Bennett C, et al. Topical treatments for cutaneous warts. Cochrane Database Syst Rev. 2012;(9):CD001781.
2. Choi Y, Kim do H, Jin SY, et al. Topical immunotherapy with diphenylcyclopropenone is effective and preferred in the treatment of periungual warts. Ann Dermatol. 2013;25(4):434-439.
3. Fernández-Morano T, del Boz J, González-Carrascosa M, et al. Topical cidofovir for viral warts in children. J Eur Acad Dermatol Venereol. 2011;25(12):1487-1489.
4. Cyrus N, Blechman AB, Leboeuf M, et al. Effect of quadrivalent human papillomavirus vaccination on oral squamous cell papillomas. JAMA Dermatol. 2015;151(12):1359-1363.
5. Wenner R, Askari SK, Cham PM, et al. Duct tape for the treatment of common warts in adults: a double-blind randomized controlled trial. Arch Dermatol. 2007;143(3):309-313.
6. Kwok CS, Holland R, Gibbs S. Efficacy of topical treatments for cutaneous warts: a meta-analysis and pooled analysis of randomized controlled trials. Br J Dermatol. 2011;165(2):233-246.
7. Ohtsuki A, Hasegawa T, Hirasawa Y, et al. Photodynamic therapy using light-emitting diodes for the treatment of viral warts. J Dermatol. 2009;36(10): 525-528.
Additional Reading
&NA;
  • Dasher DA, Burkhart CN, Morrell DS. Immunotherapy for childhood warts. Pediatr Ann. 2009;38(7): 373-379.
  • Simonart T, de Maertelaer V. Systemic treatments for cutaneous warts: a systematic review. J Dermatolog Treat. 2012;23(1):72-77.
Codes
&NA;
ICD10
  • B07.9 Viral wart, unspecified
  • B07.0 Plantar wart
  • A63.0 Anogenital (venereal) warts
Clinical Pearls
&NA;
  • No single therapy for warts is uniformly effective or superior; thus, treatment involves a certain amount of trial and error.
  • Because most warts in children tend to regress spontaneously within 2 years, benign neglect is often a prudent option.
  • Conservative, nonscarring, least painful, least expensive treatments are preferred.
  • Freezing and other destructive treatment modalities do not kill the virus but merely destroy the cells that harbor HPV.