warts%20-%20cutaneous
WARTS - CUTANEOUS
Cutaneous warts, also called verrucae, are benign proliferations of skin caused by human papillomavirus (HPV).
Most common warts on the hands and feet are due to HPV types 1, 2, 4, 27 & 57.
HPV is usually transmitted by contact with skin of an infected individual or by transmission of virus living in warm moist environment.
Autoinoculation may occur from traumatizing lesions by biting or scratching.
Incubation period is unknown but may range from months to years.

Principles of Therapy

  • Many treatment options are available but there are very few well-controlled studies testing the efficacy of treatment options
  • Patient or caregiver of child needs to be aware of advantages vs disadvantages of the treatments & that w/ any treatment, there may be recurrence of warts
  • Different types of warts may need different site-dependent treatments
    • Begin treatment w/ the least painful method especially in children
    • Aggressive & destructive treatment regimens should be given for recalcitrant lesions & areas where scarring is not a concern
  • Any of the non-pharmacological therapy or pharmacological therapy may be used alone or in combination
  • There is no single therapy that has proven to achieve complete remission of warts in all patients
  • Treatment should be made individually based on:
    • Patient’s preference
    • Patient’s desire for therapy
    • Age of the patient
    • Immunological status
    • Wart location, type, size & number
    • Degree of symptoms
    • Experience of the physician
    • Treatment availability
  • Treatment decision should be made after discussion of appropriate options w/ the patient

Pharmacotherapy

Antimitotic Agents

Bleomycin (Intralesional)

  • Reserved for recalcitrant warts or those that may be difficult to surgically excise
  • Actions: Selectively affects squamous cell & reticuloendothelial tissue
    • Inhibits DNA & protein synthesis in cells & viruses & triggers apoptosis
    • Causes acute tissue necrosis that may stimulate an immune response
  • Adverse effects: Pain, burning, erythema, swelling in the injection site, Raynaud’s phenomenon, lymphangitis, hyperpigmentation
  • Disadvantage: High cost
  • Not recommended in pregnancy, children, immunocompromised patients & patients w/ vascular disease

Retinoids

  • Tretinoin is useful for flat warts
  • Actions: Disrupt epidermal growth differentiation thereby reducing the bulk of warts
    • Alter keratinization & accelerates the clearing of warts by inducing an irritant dermatitis
    • Can downregulate human papilloma virus (HPV) transcription in affected cells
  • Administered topically or systemically; protect normal skin by using barrier cream
  • Use sun protection measures, not recommended in pregnancy

Immunomodulators

Candida Antigen (Intralesional & Intradermal)

  • Immunotherapy that is nonscarring
  • May be used on most verrucae warts especially plantar or facial warts
  • Suitable for recalcitrant warts
  • May serve as 1st-line treatment for immune individuals w/ >5 warts or >1-cm warts
  • Considered an effective 2nd-line treatment in immune individuals w/ warts that failed cryotherapy
  • Actions: Enhances the immune response at the wart site to suppress HPV infection
    • Since most people have been exposed to Candida, they will mount an immune response when Candida antigen is injected into the base of the wart
  • A study showed that 74% of the patients had resolution of injected warts & 78% of these patients also had resolution of all noninjected warts
  • Patients may experience a delayed-type hypersensitivity reaction

Cimetidine

  • H2-receptor antagonist which acts as an immunomodulating agent at high doses
  • Actions: Inhibits suppresor T-cell function while increasing lymphocyte proliferation thus enhancing cell-mediated immune responses
  • May be considered for use in recalcitrant warts & in children who cannot tolerate destructive therapy

Diphenylcyclopropenone (Diphencyprone)

  • Usually reserved for recalcitrant warts
  • May start treatment w/ 2% solution then decrease or increase as required
  • Actions: Sensitizing agent that causes a type IV delayed-hypersensitivity reaction directed against protein of viral or human origin enhancing wart regression
  • Cure rate may be approximately 80%
  • Less destructive, less time consuming, cost effective & can be used for concurrent treatment of multiple warts
  • Some patients may not tolerate the induced hypersensitivity reaction

Fluorouracil (Topical)

  • Used topically as an antiproliferative agent for flat warts
    • Used in recalcitrant warts; as an adjunct to laser excision
  • Actions: Destroys cells by inhibiting DNA & RNA synthesis
  • Effective in treating plantar warts in 92% of patients

Squaric Acid Dibutylester (SADBE)

  • A non-mutagenic contact sensitizer used to treat warts
  • Has been used for the treatment of recalcitrant warts
  • Cure rates have ranged from 58-84%
  • More expensive & less stable than Diphenylcyclopropenone (Diphencyprone)

Zinc Sulfate

  • May be used in recalcitrant warts
  • Action: Enhances the immune system
  • A clinical trial of Zinc sulfate per orem (PO) reported to show complete clearance in 87% of the treatment group compared to placebo

Keratolytics

Podophyllotoxin

  • Actions: Binds to the spindle during mitosis & blocks cellular division
  • Less effective in cutaneous warts because of poor absorption through thick stratum corneum
  • May be applied under occlusion after paring of the wart
  • Effective but w/ risk of intense inflammation, sterile pustule formation or secondary infection
  • Not recommended in children, pregnancy & lactation

Salicylic Acid

  • Safe & effective for removal of warts w/ minimal discomfort
  • Recommended as 1st-line therapy for flat warts on the face, plantar warts, flat & common warts on the hands in some guidelines
  • Actions: Slowly destroys virus-infected epidermis by dissolving the keratin layer
    • Causes mild irritation that may produce an immune response
  • Effects: Studies show approximately 75% cure rate
  • Advantages include wide availability, convenience, minimal expense, negligible pain & reasonable efficacy
  • Disadvantages: May take time before results can be observed
    • Complex instructions for home use (debride, soak, apply Salicylic acid daily)
    • Strict compliance should be observed
    • Potential risk of systemic toxicity in children
      • Can be avoided by using lower concentrations or on limited areas only
  • Still suitable for children but precautions should be made
    • Prevent them from placing the treated areas in their mouths
  • Not recommended for patients w/ peripheral neuropathy

Skin Antiseptic & Disinfectant

Silver Nitrate

  • Action: Chemically cauterizes epithelial tissues
  • Clinical efficacy is moderate
  • Caution in application should be exercised
    • May cause excessive burns & irreversible tissue staining

Virucidal Agents

Formaldehyde

  • Actions: Disrupts the upper layer of epidermal cells & possibly damages the virions
  • A study showed 80% clearance of warts
  • Avoid in patients w/ eczema & allergies

Formic Acid

  • A caustic acid
  • A study showed 92% clearance rate w/ Formic acid/needle puncture technique compared to placebo

Glutaraldehyde

  • Action: Hardens the skin & makes paring easier
  • As effective as Salicylic acid w/ >70% cure rates
  • May stain the skin brown & cause contact sensitivity

Imiquimod (Topical)

  • Showed efficacy in treating recalcitrant plantar, periungual & subungual, & flat warts
  • May be useful for lesions where scarring may be a problem, facial lesions, children w/ multiple lesions unresponsive to other therapies, & as an adjunct to laser therapy or intralesional Bleomycin
  • Action: Topical immune response modifier that stimulates the production of interferons & cytokines that produces localized immune response at the site of application
  • Less pain & trauma
    • Involves costly & lengthy treatment
  • May cause erosions, pruritus, bacterial infection, fever & scarring
  • Use sun protection measures to prevent exacerbation

Non-Pharmacological Therapy

No Treatment (Observation)

  • Cutaneous warts in immunocompetent patients cause no harm & will usually resolve w/ no treatment w/in a month to 2 years because of the patient’s natural immunity
  • May be a viable option if acceptable for the patient
  • Many patients request treatment either because of social stigma or because of painful warts
    • It is easier to treat smaller fewer warts than to wait for these to enlarge or increase

Cryotherapy

  • Works well for most warts, may be used as 1st-line therapy for flat & common warts & as 2nd-line therapy for flat & common warts on the face
    • Aggressive cryotherapy is effective & best results are achieved w/ treatment every 2 or 3 weeks
  • Recommended for light-skinned individuals
  • Liqiud nitrogen, Nitrous oxide, Carbon dioxide or a mixture of Dimethyl ester & Propane is applied to each wart until 1-2 mm of surrounding skin has turned white
  • Action: Damages the cell membranes & organelles by freezing affected cells
    • Human papilloma virus (HPV) is not destroyed but is released into the extracellular area which may produce an immunologic response
  • Patient should be made aware that pain, dyspigmentation, hemorrhagic blister, nail dystrophy, tendon & nerve damage & recurrence of the wart can occur
  • Not recommended for young children because of pain

Duct Tape Occlusion

  • Suitable for children w/ warts because it is painless, nonthreatening & inexpensive
  • Action: Host immune system is stimulated through local irritation produced by the duct tape
  • Duct tape is applied to the affected areas & removed after 6 days
    • An emery board or pumice stone is used to scrub the wart after soaking in water & left open to the air overnight
    • 6-day cycle is repeated the following morning for up to 2 months
  • A study showed 85% cure rate in children treated
  • This study did not follow patients long enough to see if recurrence occurred

Infrared Coagulation

  • Cheaper, safer & more convenient alternative to carbon dioxide (CO2) laser treatment
  • Direct application of infrared contact coagulators allows adjustable tissue necrosis w/o tissue adhesion
  • Produces remissions w/ only 10.8% recurrence rate

Lasers

Carbon Dioxide (CO2) Lasers

  • Useful in resistant warts & in treating immunocompromised patients
  • Action: Nonselective thermal tissue destruction
  • Adverse effects include postoperative pain, prolonged healing time & scarring
  • HPV has been transmitted to healthcare workers from smoke plume

Flashlamp-Pumped Pulsed Dye Laser

  • Used for facia & perianal warts in children & for recalcitrant warts
  • Action: Selective microvascular destruction of dilated capillaries in warts which results in necrotic warts that eventually slough off
  • Mixed results in treating warts
  • Causes minimal postoperative pain & heals in 2-4 weeks
  • Decreased risk of scarring & decreased risk of transmission via smoke plume to healthcare workers

Erbium:Yttrium/Aluminum/Garnet (Er:YAG) Laser

  • Has a smaller zone of thermal damage giving more accurate thermal ablation & minimal scarring
  • Warts are successfully eliminated in 75% of patients
  • HPV DNA has not been detected in the laser plume

Neodymium:YAG (Nd:YAG) Laser

  • Several reports showed remission w/ no recurrence
  • A minimal load of potential infectious laser plume & toxic pyrolysis products are removed

Potassium-Titanyl-Phosphate (KTP) Laser

  • Used for recalcitrant cutaneous warts
  • No recurrence noted when warts are treated completely

Photodynamic Therapy

  • Used to treat common warts on the hand, flat & plantar warts
  • Moderately effective w/ Salicylic acid for recalcitrant warts
  • Action: Uses 5-aminolevulinic acid (ALA) to stimulate porphyrin accumulation in the tissue which then acts as a photosensitizing agent
  • Studies show that results are equal or better than other treatment modalities w/ less or no scarring
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