TREATMENT METHODS OF CUTANEOUS WART

Cutaneous warts are a benign proliferation of keratinocytes, caused by a virus called Human Papiloma Virus (HPV). There is currently no specific antiretroviral therapy to treat HPV infection. The treatments focus primarily on destroying visible damage or cytotoxicity against infected cells.

Spontaneous remission of warts occurs in 50% of childrent within 1 year, and two-thirds within two years; spontaneous resolution in adults tends to be slower and may take up to several years or longer. Warts in patients with intact cellular immunity are the most likely to regress without therapy. Recurrence is common. Due to the benign and self-limiting nature of warts, non-therapeutic monitoring is one of the options to consider for management and if wart is treated we should avoid methods which can cause scars.

1. Topical therapy

1.1. Acid salicylic:  Topical salicylic acid is the first choice for cutaneous warts such as common wart, plane wart, and palmoplantar wart, periungual wart in both children and adults.

Mechanism of action: not well known, it exfoliates the affected epidermis and may also stimulate local immunity

Administration: Apply product containing salicylic acid to the wart, repeat this procedure on a daily basis, continue the procedure for 12 -16 weeks (stop when the lesion was revoved), brief interruption if erythema, pain, or bleeding occurs. Mild erythema in the area treated is normal. 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

Combination treatment: Salicylic often combinated with Cryotherapy, PDL, 5-FU, podpphylotoxin

Side effects: local irritation, itching, pain, bullous, salisylic poisoning but these side effects are usually mild

1.2. Silver nitrate: 

Mechanism of action: skin corrosion

Preparations containing silver nitrate with various concentrations, such as a 0.5% lotion or a liquid (20, 25, 40 or 50).

Administration: used twice weekly

Side effect: post-treatment pigmented scars have been observed. Therefore, silver nitrate should be applied with caution to avoid excessive burning and irreversible skin staining

1.3. Tretinoin: one of the first choices for plane wart.

A randomized controlled clinical trial of Ep Kubeyinje et al. On 50 infants with plane wart showed that after 12 weeks the cure rate of the tretinoin group 0.05% cream reached 84.6% compared to 32% of the control group. Mechanism of action: through regulation of differentiation and cell proliferation

Administration: tretinoin 0.05% cream applied daily until the lesion is removed.

Side effect: local stinging sensation, redness, usually during the first 2 weeks and then gradually decreasing.

1.4. Fluorourcil                                                            

Fluorouracil 5% is FDA approved for the treatment of hyperkeratosis and basal cell carcinoma. A number of randomized controlled clinical trials showed that fluorouracil was effective in cleaning up wart lesions that were unresponsive to other treatments, but the evidence was limited.

Mechanism of action: inhibit DNA and RNA synthesis and wart proliferation

Administration: 5 – Fluorouracil cream 5% applied 1-2 times / day for up to 4 weeks with / without dressing.

Side effect: erythema, edema, hyperpigmentation, hypopigmentation, ulceration, necrosis, onycholysis, or scarring.

1.5. Imiquimod: Imiquimod is an imidazoquinoline heterocyclic amine, imiquimod 5% has been approved by the FDA to treat genital and perianal genital warts in adults, light keratoses, basal cell carcinoma

Mechanism of action: local immune stimulation produces local α and cytokine interferon.

Administration:

There are many ways to use: apply 2 times a day, apply 1 time / day x 5 times / week until the lesions are clean, or apply 3 times a week (once a day). The maximum duration of use is 6 months.

To increase the effectiveness, you can prior use cryotherapy or laser or local salicylic then use imiquimod.

The reported cure rate is up to 80%. For subjects with less effective immunodeficiency.

Side effect: 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. such as erythema, edema, and erosions at the topical and peri-site sites

 1.6. Topical immunotherapy with contact allergens: Currently only squaric dibutylester acid is approve

Remission rates up to 92% have been reported.

Mechanism of action: causes local allergic contact dermatitis and stimulates immune response to enhance virus clearance from the tissue.

Administration: Apply drug (up to 3% concentration) on 1 lesion or upper arm, after 2 weeks the diluted drug concentration (0.0001–0.3%) to assess the minimum concentration that is likely to cause eczema . In case of failure to induce an eczema reaction within 1 week, a higher concentration may be used, if a severe reaction occurs, discontinue the drug 3-6 days and reduce the drug concentration the next time. Then apply the wound 2 times / week with a cotton swab. This therapy should be performed by experienced people and should not be used at home.

Side effect: general allergic contact dermatitis, changes in skin pigmentation, regional lymphadenopathy, erythema multiforme rash, urticaria.

1.7 Other topical therapy

• Zinc sulfate: The mechanism of action is to improve cellular and humoral immune responses. Double-blind clinical trial of Sharquie KE and colleagues used 10%, 5% zinc sulfate solution, and topical distilled water 3 times daily for 4 weeks for 90 patients (including 50 patients with common wart) and 40 patients with plane wart were randomly assigned, resulting in a complete response rate in 85.7%, 42.8%, 10% in those with plane wart and in 11%, 5% %, 0% corresponds to 3 research groups. The trial concluded that 10% zinc sulfate solution was a safe and effective way to treat plane wart.
• Formaldehyde solution 7% or gel 3% and glutaraldehyde 10% solution or gel: dot in lesion daily for about 3 months. The mechanism of action is to cause immediate superficial necrosis of the tissue by dehydration of the affected tissue so the damaged tissue surface should be removed before reapplying. Side effects include transient dryness, cracking, browning (glutaraldehyde only). Should use moisturizer to protect healthy tissue when used.
• Cantharidin solution 0.7%: extracted by many species of blister beetles. The mechanism of action is toxic mitochondria leading to cell death, prickly glasses, bullae. Apply 1 time, bandaged for 6 hours. After 12-24h apply the drug, bullae appear at the site of application, a few days after the bullous burst, dry, scaly. Clean lesion rate reached 80% with rice keel soles. Side effects include redness, pain, itching, post-inflammatory hyperpigmentation, scars, etc. Currently in the US, cantharidine is no longer used as a medical therapy.
• Podophyllotoxin solution 0.5% or cream 0.15%: apply twice day with  3 days /week (do not apply more than 10 cm2 skin / time, total drug volume not exceeding 0.5 ml / time), the mechanism of action is to cause tissue necrosis, prevent cell multiplication. Contraindicated for pregnant women.

2. Ablative procedures

 2.1. Cryotherapy: When topical treatments have failed, cryotherapy is considered the second-line therapy. The most common use is liquid nitrogen (-196 ° C).

Mechanism of action: cause an irreversible damage to the cell membranes obtained by freezing the infected tissue, with resulting local inflammation leading to the development of an effective cellmediated immune response

Administration:

The freezing time depends on the location and size of the common lesion until the appearance of the frozen halo surround the lesion, usually 15-20 s / replicate every 2-4 weeks for a minimum 3 months or 6 treatments.

May be use cotton-wool bud or cryospray when treatment for children and Can be used as a spray or a cotton swab when treating children and injuries near the eyes

Side effect: pain, bullous, scarring, hyperpigmentation especially in patents with dark skin. Do not apply to periungual wart because it causes dystrophy, be careful when using it on the tendon and in patients with poor blood circulation

The recurrence rate is still high (30% with rice kernels) so many treatments are performed

2.2. Other ablative procedures

Photodynamic therapy – PDT: mechanism of action is based on the uptake of chemicals (usually the amino acid laevulinic – a light sensitizer related to the porphirin pathway) of abnormal cells, the oxidation caused by light by radiation laser or non-laser irradiation to tissue takes place. The complete remission rate is from 43-75%.

Laser

• CO2 laser:  causing ablate injury. The high rate of clean lesions was 64-71% after 12 months follow-up. The periungual wart wich is difficult to remove by other methods may be particularly suitable for this treatment. Side effects include postoperative pain and scarring
• Pulsed dye laser:  energy absorption of blood vessels causing vascular destruction in the papillary dermis of the lesion thereby causing local necrosis. Clean lesion rate reaches 70-90%, pain and scarring rate is less than CO2 laser.
•  Surgical removal, shave removal or electrodessication: high success rate is 65-85%, however, the recurrence rate is high 30% and often leaves scars and pain lasting after the procedure.

3.Some intralesional therapies

3.1 Bleomycin: is a water-soluble glycopeptide antibiotic with cytotoxic effect, used to treat warts unresponsive to other treatments.

• Mechanism of action: inhibits DNA synthesis thereby inhibiting cell division and growth.
• Studies using bleomycin 250-1000 U / ml did not find higher concentrations for higher benefits. Response rates of 31-100% were reported.
• Administration: inject bleomycin 1 U / ml (0.1-0.2 ml) into the lesions, most lesions respond after 1-2 treatments.
• Side effects: pain during and after the injection (so local anesthesia is needed), scarring, pigment changes, nail damage. Bleomycin should not be used in pregnant women because significant systemic absorption after intravascular injection had been reported.

3.2 Interferon: is a group of natural proteins produced by the cells of the immune system in humans and most animals against foreign agents such as viruses, bacteria, parasites and cancer cells.

• Administration: intralesion 1 million units / lesions (no more than 5 lesions / time) 3 times / week for 3 weeks, 2 treatments 12-16 weeks apart.
• The studies using interferon had shown a 50-62.4% reduction in injury rates, but data are limited.
• Side effects are usually mild, including pseudo-influenza symptoms, gastrointestinal side effects such as vomiting, nausea, increased leukocytosis, elevated liver enzymes, depression.

3.3 Other therapies reported effective include 5 – FU, kẽm sulfate 2%, intralesion…

4. Some systemic therapies

4.1 Cimetidine: an class 1- H2 receptor antagonist

• Mechanism of action: increase in cell-mediated immunity
• Administration: studies using different doses of 25-40 mg / kg / day in 2-3 divided doses or 400 – 800 mg 3 times / day, up to 2400 mg / day. Statistical data of 4 placebo-controlled clinical trials showed a cure rate of 36% compared to 22% for the control group.
• Side effects: no significant side effects have been reported, mainly gastrointestinal side effects.

4. Mechanism of action: stimulates immune response.

• Administtation: 5 mg / kg / day for 3 consecutive days every 2 weeks for up to 5 months, shown a response rate about 60%.
• Side effects: prolonged prothrombin time, headache, nausea, vomiting, erythema, dyspnea, hypertension.

4.3 Acitretin Using 1 mg/kg/day for 3 months gives 80% output. Use in case of widespread wart

4.4  Zinc sulfate: Using 10 mg/kg/day up to 600 mg/day for 2 months gives 78-80%, using in case of  widespread warts, 50% for recurrent warts, 50% for normal warts.

Author: Dr. Phạm Diễm Hương

Publisher: Social Work Department