By Gary M. White, MD
Verrucous lesions on the lip and fingers. (Don't bite the wart!)
Warts or verrucae are skin lesions caused by infection by human papillomavirus (HPV).
Warts are so successful because they "hide" from the immune system.
Warts come in many shapes and sizes. The most common is the hyperkeratotic, verrucous papule on the hands or feet of a child. Flat warts are slightly raised, flat papules or small plaques. Occasionally, they may resemble nevi. Many warts are exophytic (stick out), but lesions on the soles are usually endophytic (extend into the skin) because of the constant pressure. Warts commonly occur about the nails (see periungual), especially in children who bite or pick their nails. Warts do not show fingerprints, in contrast to calluses.
Darker-skinned patients get warts less commonly which is fortunate given that cryotherapy easily induces white spots after therapy.
If located on the sole, be sure to confirm the diagnosis by paring. A wart has black dots; a corn has a clear center. Verrucous lesions that resist treatment should be biopsied. Occasionally a squamous cell carcinoma or even an amelanotic melanoma may be found. Subungual lesions in an adult should raise particular concern and prompt biopsy sooner rather than later (see subungual squamous cell carcinoma).
No treatment is needed for these benign lesions. However, they are contagious, both to the patient and to others.
The mainstay of treatment is cryotherapy performed every 2-3 weeks. A single 10 second freeze seems optimum, based upon studies (see below). A second freeze-thaw added benefit only for plantar warts in one study [BJD 1994;131;883]. Waiting more than 3 weeks between treatments allows the wart time to grow back. Two weeks between treatments seems to be optimum for most patients. However, one study of external genital warts [Dermatologica Sinica 2014;32;154-156] found that double freeze-thaw every 7-8 days required fewer sessions and cleared quicker than every 14-21 days.
It is not unusual for the patient to need 6-10 treatments in order to clear the warts. Thus, the patient should be told that one treatment rarely does it--multiple treatments are needed.
An interesting study compared the traditional freeze-thaw (freeze until the wart and a surrounding 1-2 mm halo of normal skin turns white and then stop) to a 10-second freeze (same as traditional, but keep spraying to keep white for 10 seconds) each done every 2 weeks for a maximum of 5 weeks [BJD 2001;145;554]. The 10-second freeze was significantly more effective and cleared 64% of non-defaulters compared to 39% in the traditional group. There was more pain, blistering and other side effects, however. Some patients are exquisitely sensitive to cryotherapy and this seems to be idiosyncratic. Thus, perhaps the best approach is to use the traditional method on the first visit and move up to 10 seconds on subsequent visits as tolerated. An alternative published approach is to remove the tip from the cryogun, making it a cryoblast. This increased clearance rates in one study.
The use of the spray gun can be frightening to children. A good alternative is to use a cup of the liquid nitrogen to soak a hemostat or forceps for fifteen seconds, then grab the wart for ten seconds. There is no scary spray, nor dripping of the liquid nitrogen (compared with using a cotton-tipped applicator).
Immunotherapy with candida antigen is a safe and effective treatment of warts in children. The main drawback is the pain and fear experienced by the patient. In one retrospective review of 220 children who were treated with intralesional injection of Candida every 3 weeks [Pediatr Dermatol 2015 Sep 07], 70% of treated wart cleared in an average of 2.73 treatments. The cure rate is high, but all warts may need to be treated for complete clearing.
Using the MMR vaccine instead of the Candida antigen seems just as effective. In one study, the MMR vaccine 0.5 cc was injected intralesionally into each wart in the MMR group, whereas normal saline was used in the second group. These injections were repeated every 2 weeks for a maximum of 3 injections. Eighteen of 24 patients cleared in the MMR group (75%) vs. only 6 of 24 in the saline group (25%) [Adv Biomed Res. 2014 Mar 31;3:107].
In a recent study, intralesional injections of 0.2- to 0.5-mL vitamin D3 solution (600,000 IU; 15 mg/mL) at 3-week intervals were used to treat recalcitrant warts in 60 patients. The majority of patients (90%) had complete clearing. Complete resolution required an average of 3.66 injections. Of the 35% of patients with distant warts, all experienced complete resolution of these in addition to resolution of the primary lesion. Up to 5 warts were injected at each visit [J Cutan Med Surg 2017 Apr 06].
Intralesional bleomycin can be highly efficacious, even for treatment-resistant warts. Usually the 1 U/ml concentration is used, and the wart injected till it blanches. 0.1-0.2 ml per wart is typical. Pain can be significant and last up to a week. The patient should be told to expect the wart to turn black several days after treatment and then falls off in 2-4 weeks. Treatment may be done every 3 weeks, but at most 2 treatments are usually needed. Warts on the fingers may not be best suited for Bleomycin as nail dystrophy, Raynauds and even digital necrosis are rare side effects there.
5-FU may be applied to a wart nightly. (Off label). In a study of 39 children treated with 5-FU once or twice daily under occlusion for 6 weeks [Pediatr Dermatol. 2009 May-Jun;26(3):279-85] the following was found: "Eighty-eight percent of treated warts improved after 6 weeks of treatment, and 41% of subjects had complete resolution of at least one wart. Treatment response did not differ between once or twice daily applications. Tolerability and patient satisfaction were excellent. No subject had clinically significant blood levels of 5-fluorouracil. At 6 month follow-up, 87% of complete responders had no wart recurrence. Topical 5% 5-fluorouracil is a safe, effective, and well-tolerated treatment for warts in children."
5-FU can cause pigmentation of the nail (usually reversible). See periungual warts. Some combine 5-FU with imiquimod, one in the morning and one at night.
Occluding a digital wart with duct tape for 6.5 days to make it "mushy" (and some theorize better allowing the immune system to recognize the wart) can be effective. On the seventh day, the duct tape is removed and the wart pared down and allowed to dry. The tape is then reapplied. Repeat as necessary as long as progress is being made.
The CO2 or pulsed dye laser is often employed in recalcitrant cases.
3% cidofovir cream applied BID with occlusion for a period of about 12 weeks completely cleared 53% of recalcitrant warts in one study [JEADV 2016;30;1218]. This included patients with genital, periungual and plantar warts. Local irritation erythema and/or pruritus occurred in about 14% of patients. Topical 3% cidofovir has also been used with success in immunocompromised children applied daily and occluded [PD 2017;34;e24].
Imiquimod has been used in recalcitrant warts in various locations in children. Sixteen of 18 children cleared with BID therapy after a mean of 6 months of use [Ped Dermatol 2002 May-Jun;19(3):263-6]. In another study compared with cryotherapy every 2 weeks, plantar warts in children were more likely to clear with imiquimod and salicylic acid compared with cryotherapy alone (83% vs 30% clearance at 3 months) [J Dermatolog Treat 2016 Jan 01;27;80-82]. Specifically the parentrs applied 5% imiquimod every morning for 5 days/week and filling of warts every evening followed by 15% salicylic acid.
The topical application of squaric acid induces an allergic contact dermatitis and can clear recalcitrant warts in children. A retrospective chart review [Pediatr Dermatol. 2015 Jan-Feb;32(1):85-90] found that 40 of 48 (83%) patients in whom treatment outcomes could be obtained reported complete resolution of their warts. Age range was 3-18 years, and the average treatment duration was 6-12 months. Various protocols are used (e.g., The Permanente Medical Group).
One study showed 24 of 25 plantar warts cleared in 37 ± 19 (56-17) days with topical adapalene 0.1% gel applied twice daily under occlusion using plastic wrap [Indian Journal of Dermatology, Vol. 60, No. 1, January-February 2015, pp. 102].
One may pare the top of the plantar wart and then treat with salicylic acid and 5-fluorouracil plaster in the morning and imiquimod under occlusion nightly for 8 to 12 weeks.
Topical, oral and intralesonal zinc have been used successfully for warts as reported in a variety of small studies. Indeed, zinc deficiency appears to be associated with treatment-resistant warts [J Coll Physicians Surg Pak. 2010 Feb;20(2):83-6]. Measuring serum zinc and if low, treating with one of the above regimens appears reasonable. Nausea is the main potential side effect of oral zinc.
In one placebo-controlled trial, oral zinc at a dose of 10 mg/kg/day up to 600 mg/day resulted in complete clearance of warts in 20 patients (86.9%) after 2 months of treatment compared with zero in the placebo group. However, it must be noted that all patients were zinc deficient and according to the article "the response to treatment was directly related to the increment in serum zinc level" [Br J Dermatol 2002;146:423]. In another randomized study [JAAD 2009;60;706], 78.1% (25/32) of patients cleared after a 2-month course of treatment with zinc sulfate 10 mg/kg/day up to 600 mg/day compared to 13% (3/23) in the control group.
In one study of vulvar warts, the addition of 400 mg oral zinc sulfate daily to crotherapy, podophyllin or imiquimod did not speed clearance, but did reduced recurrence [J Obstet Gynaecol Res. 2014 Oct;40(10):2110-3].
Pulsed dye laser induces the lowest rate of recurrence of plantar warts, as compared to other treatments (e.g. freezing, CO2, keratolytics). There is a higher risk of relapse of non-genital warts in subjects older than 25 years and a 5-fold increased risk in smokers, as compared to non-smokers. Smoking is also related to time to initial healing and to time to complete healing at follow-up [JEADV 2017;31;712].
Periungual, a very common location.
This wart is regressing.
Filiform wart on the elbow.
Cantharadin treatment can result in the wart becoming larger with annular and linear forms (see donut wart).