Warts%20-%20cutaneous Treatment

• 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

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

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