1. Pharmacology-4 PHL 425 By Dr. Yieldez Bassiouni

2. Anti-Warts Drugs

3. Anti-Warts Drugs, Introduction  Cutaneous warts are benign epidermal proliferations caused by human papillomavirus (HPV) infection  Papillomaviruses (Small DNA virus) comprise a family of viruses that are host- species specific. Thus, HPV causes disease only in humans, infecting epithelial tissues and mucous membranes  Cutaneous warts are one of the most common skin conditions affecting children  Transmission of warts occurs from direct person-to-person contact or indirectly by fomites  Swimming pools and bathrooms are common areas for the spread of warts if the skin is macerated and touches rough surfaces  Once HPV has infected the skin, autoinoculation can occur by scratching, shaving or traumatizing the skin  Previously infected patients have a higher risk for development of new warts than those never infected

4. Anti-Warts Drugs, Introduction  Types of warts; genital or non genital (venereal or non- venereal)  Nongenital warts occur in 7% to 10% of the general population, with the incidence peaking between the ages of 12 and 16 years  Warts occur equally in both sexes and are among the three most common dermatoses treated  Owing to natural immunity, approximately 23% of warts regress spontaneously within 2 months, 30% within 3 months and 65% to 78% within 2 years  The rate of clearance is influenced by factors such as viral type, host immune status, extent and duration of warts

5. Anti-Warts Drugs, Introduction  The clinical picture of cutaneous warts differs by specific location on the body: Plane or flat warts are smooth flat topped papules with minimal scaling and only slight elevation, most often on the face. They are more common in children and young adults. They generally cause no symptoms but can be difficult to treat Verruca vulgaris (common warts) are hyperkeratotic, exophytic and dome- shaped papules or nodules especially located on fingers, hands, knees, elbows or any other sites of trauma. Generally, they are asymptomatic but sometimes cause mild pain

6. Anti-Warts Drugs, Introduction Plantar warts are warts on the sole of the foot  They can be painful due to their callused, endophytic papules that have deeply penetrating sloping sides and a central depression Numerous coalesced warts on the plantar surface will form a tile-like pattern known as mosaic warts. As with other plantar warts, they are often tender

7. Anti-Warts Drugs, Introduction  Filiform warts are long, frondlike growths usually on the eyelids, face, neck, or lips. They are usually asymptomatic. This morphologically distinct variant of the common wart is benign and easy to treat  Periungual warts appear as thickened, fissured cauliflower-like skin around the nail plate. Patients frequently lose the cuticle, and are susceptible to paronychia. These warts are more common in patients who bite their nails

8. Genital warts The most common sexually transmitted disease worldwide Most people do not know they have it (generally asymptomatic) Anogenital warts occur in the perineum and on the genitalia or in the genital tract ► Some types are considered “low risk”, other types are considered “high risk” and can cause pre-cancerous lesions and can lead to cancer of the cervix, anus and other genital areas ► > 90% of anogenital warts resolve within 2 years, persistent infection with high-risk HPV subtypes is the main cause of cervical and anal cancer ► Parts of the viral DNA link to specific genes in human cells, transforming them into cancer cells

9. Treatment of Warts  Extragenital warts in people who are immunocompetant are harmless and usually resolve spontaneously within months or years owing to natural immunity  In view of this, a policy of not treating them is often advised. However there is considerable social issues associated with warts on the face and hands, and they can be painful on the soles of the feet and near the nails. Therefore, many patients request treatment for their warts  The American Academy of Dermatology developed criteria for the indications for wart treatment including: 1)the patient’s desire for therapy 2)symptoms of pain, bleeding, itching or burning 3)disabling or disfiguring lesions 4)large numbers or large sizes of lesions 5)the patient’s desire to prevent the spread of warts to unblemished skin of self or others 6)an immunocompromised condition  Anogenital warts should receive special consideration and warrant vigilance for other sexually transmitted diseases

10. Treatment of Warts The goal of wart treatment is to destroy or remove the wart without creating scar tissue, which can be more painful than the wart itself. Start with the least painful, least expensive, and least time-consuming methods. Reserve the more expensive and invasive procedures for refractory warts. Home treatment is often effective in curing common warts (Salicylic acid).

11. Treatment of Warts, contd.  Wart paints should not be used to treat facial warts because of severe irritation and a potential for scarring  Salicylic acid (SA) is a first-line therapy for warts  It is a keratolytic therapy with a mechanism of action that slowly destroys virus- infected epidermis and may cause an immune response from the mild irritation caused by the salicylic acid  It is prepared in concentrations from 10% to 70%.  Over-the-counter preparations are available as 17% SA combined in a base of flexible collodion or as a 40% salicylic acid plaster patch  The advantages of over-the-counter SA include convenience, minimal expense, negligible pain and reasonable effectiveness  Disadvantages are that results require weeks to months of treatment, and the patient must strictly adhere to instructions  Side effects can include occasional contact dermatitis due to colophony in the collodion base. There is also a potential risk of systemic toxicity in children that can be avoided if lower concentrations or limited areas of treatment are used

12. Home treatment is effective in curing common warts (Salicylic acid) Salicylic acid for application to all kinds of warts, from tiny ones to great, big lumpy ones Salicylic acid is a keratolytic medication, which means it dissolves the protein (keratin), which makes up most of the wart and the thick layer of dead skin that tops it Salicylic acid comes either as a liquid to paint on the wart or as a plaster to be cut out and placed on the wart tissue The area with the wart should be soaked in warm water for 5-10 minutes The wart should then be pared down with a razor Do not make the wart bleed Apply the salicylic acid preparation to the wart tissue This could be repeated 3 times a week until full recovery

13. Treatment of Warts A) Destructive measures: 1. Physical 2. Chemical B) Immuno-modulatory measures

14. Physical methods Electrocautery: use of electric current to burn off the warts Cryocautery: use of liquid nitrogen to freeze off the warts Laser: a laser beam or intense lights to destroy the warts Surgical excision is usually reserved for warts that haven't responded to other therapies (scarring).

15. Freezing (cryotherapy, or liquid nitrogen therapy) Cryotherapy is used to deep freeze the wart tissue When liquid nitrogen is applied to the wart, the water in the cells expands, thus exploding the infected tissue The exploded cells can no longer hide the human papillomavirus from the body's immune system The immune system then works to destroy the virus particles Best for pregnant women

16. Laser Therapy Lasers are simply very intense light sources This light has an enormous amount of energy that heats the tissue enough that it vaporizes Pulse dye laser or carbon dioxide (CO2) laser

17. 2. Chemicals must be applied by a trained health care provider to destroy warts Trichloro- acetic acid, Glacial acetic acid caustic compounds that cause tissue necrosis Podophyllin is a cytotoxic compound (best for genital warts) Podophyllotoxin is a purified ingredient of podophyllin

18. B) Immune response modifiers  Local immune enhancers that stimulate production of other interferons or cytokines  Interferon -alfa is a naturally occurring cytokine with antiviral and immunomodulatory effects. Can be injected directly into warts  Imiquimod: a topical cream or gel that helps the body's immune system fight the wart virus through stimulation of T-helper cells for genital warts

19. Antiviral Agents Cidofovir is active against all DNA viruses Topical cidofovir 1% gel can be applied to the lesions at bedtime and left on overnight, three times a week for up to 16 weeks Because cidofovir possesses direct antiviral effects, topical cidofovir does not require a competent immune system to be effective and therefore has a greater benefit in patients with HIV infection

20. Other therapies Tretinoin disrupts wart's skin cell growth. (cream or an oral medication) Bleomycin used with caution to kill the virus. Risks of this therapy include nail loss and damage to the skin and nerves 5-Fluorouracil is a topical chemotherapeutic agent Benzalkonium

21. Best wishes