Wart



A wart is generally a small, rough growth, typically on a human’s hands or feet but often other locations, that can resemble a cauliflower or a solid blister. They are caused by a viral infection, specifically by human papillomavirus 2 and 7. There are as many as 10 varieties of warts, the most common considered to be mostly harmless. It is possible to get warts from others; they are contagious and usually enter the body in an area of broken skin. They typically disappear after a few months but can last for years and can recur.

Types
A range of types of wart have been identified, varying in shape and site affected, as well as the type of human papillomavirus involved. These include:
 * Common wart (Verruca vulgaris), a raised wart with roughened surface, most common on hands, but can grow anywhere on the body;
 * Flat wart (Verruca plana), a small, smooth flattened wart, flesh-coloured, which can occur in large numbers; most common on the face, neck, hands, wrists and knees;
 * Filiform or digitate wart, a thread- or finger-like wart, most common on the face, especially near the eyelids and lips;
 * Genital wart (venereal wart, Condyloma acuminatum, Verruca acuminata), a wart that occurs on the genitalia.
 * Mosaic wart, a group of tightly clustered plantar-type warts, commonly on the hands or soles of the feet;
 * Periungual wart, a cauliflower-like cluster of warts that occurs around the nails.
 * Plantar wart (verruca, Verruca pedis), a hard sometimes painful lump, often with multiple black specks in the center; usually only found on pressure points on the soles of the feet;

Pathology and etiology


Warts are caused by the human papilloma virus (HPV). There are about 130 known types of human papilloma viruses. HPV infects the squamous epithelium, usually of the skin or genitals, but each HPV type is typically only able to infect only a few specific areas on the body. Many HPV types can produce a benign growth, often called a "wart" or "papilloma", in the area they infect. Many of the more common HPV and wart types are as follows:


 * Common warts - HPV types 2 and 4 (most common); also types 1, 3, 26, 29, and 57 and others.
 * Cancers and Genital dysplasia - "high-risk" HPV types are associated with cancers, (cervical cancer and can also cause some vulvar, vaginal, penile, anal and some oropharyngeal cancers. "low-risk" types are associated with warts or other conditions.  )
 * High-risk: 16, 18 (cause the most cervical cancer); also 58, 33, 45, 31, 52, 35, 39, 59, and others.


 * Plantar warts (myrmecia) - HPV type 1 (most common); also types 2, 3, 4, 27, 28, and 58 and others.
 * Anogenital warts (condylomata acuminata or venereal warts) - HPV types 6 and 11 (most common); also types 42, 44 and others.
 * Low-risk: 6, 11 (most common); also 13, 44, 40, 43, 42, 54, 61, 72, 81, 89, and others.


 * Flat warts - HPV types 3, 10, and 28.
 * Butcher's warts - HPV type 7.
 * Heck's disease (Focal epithelial hyperplasia) - HPV types 13 and 32.

Histopathology
Common warts have a characteristic appearance under the microscopic. They have thickening of the stratum corneum (hyperkeratosis), thickening of the stratum spinosum (acanthosis), thickening of the stratum granulosum, rete ridge elongation, and large blood vessels at the dermal-epidermal junction.

Prevention
Gardasil is a HPV vaccine aimed at preventing cervical cancers and genital warts. Gardasil is designed to prevent infection with HPV types 16, 18, 6, and 11. HPV types 16 and 18 currently cause about 70% of cervical cancer cases, and also cause some vulvar, vaginal, penile and anal cancers. HPV types 6 and 11 are responsible for 90% of documented cases of genital warts. Unfortunately the HPV vaccines do not currently prevent the virus strain responsible for verrucas.

Treatment
There are many different treatments and procedures associated with wart removal. One review of 52 clinical trials of various cutaneous wart treatments concluded that topical treatments containing salicylic acid were the best supported, with an average cure rate of 75%, compared with 48% for the placebo in six placebo-controlled trials including a total of 376 participants.It can also be controlled by laser therapy The reviewers also concluded that there was little evidence of a significant benefit of cryotherapy over salicylic acid or duct tape.

One complicating factor in the treatment of warts is that the wart may regrow after it has been removed.

Prescription medications
Treatments that may be prescribed by a medical professional include
 * Application of podophyllum resin paint [podophyllum resin I.P.'66 (20% w/v), benzoin I.P. (10% w/v), aloes I.P. (2% w/v), isopropyl alcohol I.P. to make (100% v/v)]
 * Imiquimod, a topical cream that helps the body's immune system fight the wart virus by encouraging interferon production. Approved by the U.S. Food and Drug Administration (FDA) for genital warts. The drug is very expensive.
 * Cantharidin, a chemical found naturally in many members of the beetle family Meloidae which causes dermal blistering. Either used by itself or compounded with podophyllin. Not FDA approved, but available through Canada or select US compounding pharmacies.
 * Bleomycin, not US FDA approved. One or two injections used. It can cause necrosis of digits and Raynaud syndrome.  This drug is expensive, USD $200–300 per vial.
 * Dinitrochlorobenzene (DNCB), like salicylic acid, this is applied directly to the wart. Studies showed this method was effective with a cure rate of 80%. But DNCB must be used much more cautiously than salicylic acid; the chemical is a known mutagen, able to cause genetic mutations. So a physician must administer DNCB. This drug induces an allergic immune response resulting in inflammation that wards off the wart-causing virus.
 * Fluorouracil, which inhibits DNA synthesis, is being used as an experimental treatment. It is applied directly to the wart (especially plantar warts) and covered (for example: with tape).  This treatment is combined with the use of a pumice stone, but tends to work very slowly.
 * Salicylic acid can be prescribed by a dermatologist in a higher concentration than that found in over-the-counter products.  Examples include a topical solution marketed by Elorac, Inc. under the trade name Durasal.

Procedures

 * Keratolysis, of dead surface skin cells usually using salicylic acid, blistering agents, immune system modifiers ("immunomodulators"), or formaldehyde, often with mechanical paring of the wart with a pumice stone, blade etc.
 * Electrodesiccation
 * Cryosurgery, which involves freezing the wart (generally with liquid nitrogen), creating a blister between the wart and epidermal layer, after which the wart and surrounding dead skin falls off by itself. An average of 3 to 4 treatments are required for warts of thin skin.  Warts on calloused skin like plantar warts might take dozens or more treatments.
 * Surgical curettage of the wart;
 * Laser treatment - often with a pulse dye laser or carbon dioxide (CO2) laser. Pulse dye lasers (wavelength 582 nm) work by selective absorption by blood cells (specifically haemoglobin).  CO2 lasers work by selective absorption by water molecules.  Pulse dye lasers are less destructive and more likely to heal without scarring.  CO2 laser works by vaporizing and destroying tissue and skin.  Both laser treatments can be painful, expensive, and can cause scarring.  CO2 lasers will require local anaesthetic, while pulse dye laser might need conscious sedation.  It takes 1 to 4 treatments.
 * Infrared coagulator - an intense source of infrared light in a small beam like a laser. This works essentially on the same principle as laser treatment.  It is less expensive.  Like the laser, it can cause blistering pain and scarring.
 * Injection of Candida, mumps, or Trichophyton antigens at the site of the wart, which stimulates the body's immune system. While the drug is approved by the U.S. Food and Drug Administration to test the immune system, it is not yet approved as an effective wart treatment.

Over-the-counter
There are several over-the-counter options. The most common ones involve salicylic acid. These products are readily available at drugstores and supermarkets. There are typically two types of products: adhesive pads treated with salicylic acid or a bottle of concentrated salicylic acid solution. Removing a wart with salicylic acid can be done by cleaning the area, applying the acid, and removing the dead skin with a pumice stone or emery board. It may take up to a year to remove a wart.

Another product available over-the-counter that can aid in wart removal is silver nitrate in the form of a caustic pencil, which is also available at drug stores. In a placebo-controlled study of 70 patients, silver nitrate given over nine days resulted in clearance of all warts in 43% and improvement in warts in 26% one month after treatment compared to 11% and 14%, respectively, in the placebo group. The instructions must be followed to minimize staining of skin and clothing. Occasionally pigmented scars may develop.

Cryosurgery or cryotherapy devices using freon refrigerants are inexpensive. A disadvantage is that the sponge applicator is too large for small warts, and the temperature achieved is not nearly as low as with liquid nitrogen. Complications include blistering of normal skin if excess freezing is not controlled.

Several randomized controlled trials have found that zinc sulfate, consumed orally, can bring to the disappearance of warts, using typically about 2.5 mg/kg/day elemental zinc (large amounts of zinc may cause a copper deficiency ). Other trials have found that topical zinc sulfate solution or zinc oxide are also effective.

Cimetidine has also been shown to work in the removal of warts in certain studies, but not in several others. While the exact mechanism is unknown, it is thought to heighten the state of the immune system and 'alert' the body about the wart. It seems to work better on flat warts than others. Research has shown both positive and negative results as to its effectiveness, the most being 80% effective while ingesting 30 mg/kg/day from 6–8 weeks.

Duct tape occlusion therapy
Duct tape occlusion therapy (DTOT) involves placing a piece of duct tape over the wart(s) for six days, followed by soaking the area in water and scraping it with a pumice stone or emery board. There is conflicting evidence as to whether or not DTOT is an effective wart therapy.

The study cited above had 9 patients lost to the follow-up from the original 61 patients entered. In contrast to the flaws (15% of subjects lost to the follow-up) and favorable results of the above study, a more stringent study of 103 children found no benefits from transparent duct tape. The evaluators were blinded during treatment for the most part, a placebo (corn pad) was used and there were no patients lost to the follow-up. After six weeks, rates of wart resolution were similar in the duct tape and corn pad groups and much lower than the rates seen in the earlier trial.

Above two studies are compared by Jeanne Van Cleave, MD; Alex R. Kemper, MD, MPH, MS; Matthew M. Davis, MD, MAPP and conclusions can be drawn that the population size of 100 was insufficient to prove non-meaningful therapy. In fact with a population of 350 and the same percentage results (6% healed in placebo, 16% in duct tape group), a sample of that size would have given them more than 80% statistical power; importantly, the same results they described would have led them to reject the null hypothesis at P<.05. Although such a study would have been more expensive, it would have provided a better test of the null hypothesis.

A similar trial comparing duct tape with a control treatment with a moleskin pad in 90 adults also found no difference in the rate of wart resolution at the end of two months (21 versus 22 percent). However, the median age in this study was 54 years, and transparent tape was used, which contains no rubber found in the standard gray variety.