Differential diagnosis

Warts can be mistaken for any other benign or malignant overgrowths/ tumors, and vice versa, benign and malignant overgrowths or tumors of the skin and mucosa may take on the appearance of warts. Thus, warts can be mistaken for a callus, a nevus, acrochordons, seborrheic keratoses, actinic keratoses, a squamous cell carcinoma or a melanoma (when pigmented). On the other hand, cases of depigmented and verrucous melanomas and warty-appearing squamous cell carcinomas have been reported in the literature. Perianal verrucous epidermal nevi can be mistaken for perianal warts [57]. Pseudoverrucous nodules, seen in association with incontinence, resemble condyloma as well [58]. Although these entities are disparate, the association of the wart virus with tumor promotion may mean that verru-cous carcinomas and warts can exist side by side in a lesion. Thus, biopsy for confirmation is required in a normal-appearing wart if biological behavior or response to therapy is atypical.

A variety of drug options exist for HPV infections in childhood. Choice of treatment depends on the age of the patient, the location of the warts, the number of warts, duration of infection, underlying illnesses and patient preference.

For warts, there are six types of treatments that can be used: destructive, immunological, psychological, sclerosant, antiviral and anti-mitotic. Often

Table 6. Overview of treatments for extra-genital and genital HPV infections

Extra-genital

Genital

Destructive

Cryotherapy

X

X

Cantharidin

X

X*

Duct tape

X

Garlic

X

Podophyllin

X

Photodynamic therapy

X

Salicylic acid

X

X*

Surgery

X

X

Immunotherapy

Antigen injection (Candida, mumps)

X

Cimetidine

X

X

Imiquimod

X+

Squaric acid immunotherapy

X

X*

Interferon

X

Vaccination

X

Vascular

Bleomycin

X

Pulsed dye laser

X

X

Psychological

X

Anti-mitotic

5 Flourouracil

X

X*

*Use of these substances in the genital area in young children should be limited and observed closely by a physician

+Treatment regimen and efficacy differ significantly between genital and extra-genital disease

*Use of these substances in the genital area in young children should be limited and observed closely by a physician

+Treatment regimen and efficacy differ significantly between genital and extra-genital disease the clinician will choose moderately effective methods of therapy that have few side effects or no pain over a very effective but painful regimen of therapy.

Among the destructive methods, salicylic acid has the best clinical trial data supporting its usage, with a number of placebo-controlled trials documenting a 50-75% rate of cure with 6 weeks usage [59]. On the other hand, liquid nitrogen application every 2-3 weeks is generally 60-76% effective [60, 61]. Liquid nitrogen is painful and may induce hemorrhagic blisters [62-64]. Nerve block may reduce the pain associated with liquid nitrogen [65]. Cantharidin has been described as a fairly effective therapy for warts. Donut warts around the lesion tend to be very common with this drug.

Cantharidin is about as effective as liquid nitrogen and is best in young children as a therapy because its use is rarely associated with pain. Rarely, lymphedema can be seen with cantharidin application [24, 66]. Usage of cantharidin mixed with other agents such as podophyllin is inadvisable in pediatric practice. Topical garlic has been used on a nightly basis as a homeopathic method of wart therapy and works over a 6-week time period. It is well tolerated and very cheap [67]. Garlic is a nitric oxide releaser and a vesicant, and may be effective due to both of these properties [68, 69].

Occlusion of wart therapies is a standard mechanism of enhancing drug efficacy. Recently, a small study documented the efficacy of weekly re-applied duct tape alone as a therapy for non-acral warts. The success rate was 85% in 6 weeks with limited side effects [61].

Immunotherapies hasten immune recognition of HPV by the body. Imiquimod 5% cream is an immune response modifier approved in the United States for the treatment of genital warts. When applied to the skin, Imiquimod induces production of interferon-a, TNF-a, IL-1, IL-6, and IL-8. Many small case series or single case reports have anecdotally reported a variety of successful regimens of Imiquimod application for common warts in children. The most effective regimen reported has been a twice-daily application. Usage under a diaper is inadvisable, as severe ulceration may result [70-76]. Other topical immunotherapies used in children include diphencyclopropenone (DCP) and squaric acid (SADBE) [77-79]. SADBE has been described for office or home usage, while DCP is generally used in-office [80-82]. Clearance rates in published studies have varied from 58-90% with eczematous side effects being common and rare urticaria [79]. Oral cimetidine in standard pediatric dosage can enhance wart clearance, but works in only about half of patients treated [83, 84]. Genital warts can also respond to cimetidine [85]. Intralesional injections of mumps and Candida antigen are painful and cause flu-like side effects but may induce more than 60% wart clearance [86-90]. Interferon injections can also be used as immunotherapy for warts and condyloma [91, 92].

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