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Combined Cryotherapy/70 % Salicylic Acid Treatment for Plantar Verrucae

Robert L. van Brederode, DPM, 1 and Elliott D. Engel, DPM2


Although common, warts are inconsistently treated by any single method. The authors present a review of the literature for various treatments with regard to the methodology and success rate of each treatment modality. The authors also present a therapeutic regimen of combined cryotherapyl 70% salicylic acid. This treatment involves in-office application of the cryogenic agent and daily application of 70% salicylic acid by the patient. The cryotherapy was combined with daily patient application of salicylic acid to increase destruction of the verruca. In a study of 29 patients with 65 warts, the authors found this method successful in 58 warts in 25 patients, showing a 89.2% rate of eradication of verrucae in 86.2% of patients. The method is recommended due to its consistent efficacy in the patient population, and its relatively gentle and noninvasive approach. (The Journal of Foot & Ankle Surgery 40(1):36-41, 2001)
Key words: acid, cryotherapy, verruca

Plantar verrucae are one of the most common pathologies seen today by the podiatric physician. These benign lesions, or warts, are caused by the human papilloma virus (HPV). Over 65 versions of HPV have been found (I), but types I, 2, and 4 most frequently cause verrucae on the foot (I, 2). HPV tends to affect keratinized skin. Transmission of HPV often happens when skin comes in contact with the virus in a locker room or communal restroom. Warts can also be transmitted from person to person (3), especially in close circles like families (I). Some sort of trivial trauma is a common factor in the transmission of the virus. The key is that the trauma must be significant enough to allow the virus to penetrate the epidermis. The mechanism of viral infection is to alter the surface of the cell membrane and produce immunogens. The infection is combated by the body's cell-mediated immunity, mainly the T cells (4). Common features can aid in the diagnosis of verrucae plantaris. Warts occur most often in the fall and winter months, and are very common in adolescents (5). Plantar verrucae represent 30% of cutaneous warts. Anatomically, warts are frequently found on areas where higher pressures are exerted like the toes, metatarsal heads, and heels (1). One can identify a wart by noticing a change in the
Address correspondence to: Elliott D. Engel, DPM, 406 Norristown Road, Suite F, Horsham, PA 19044. I Submitted as a Fourth Year Student, Temple University School of Podiatric Medicine; currently First Year Resident at Christiana Care Health Services, Wilmington Hospital, Wilmington, DE. 2 Private practice, Horsham, PA. Received for publication July I, 1999; accepted in revised form for publication September 3, 2000. The Journal of Foot & Ankle Surgery 1067-2516/01/4001-0036$4.00/0 Copyright 200 I by the American College of Foot and Ankle Surgeons

regular papillary skin lines, and observing its own independent vascular source (5). Pain from lateral squeezing will differentiate a verrucae from an intractable plantar keratosis, which typically elicits pain from direct vertical pressure. When these lesions resolve, normal dermatoglyphics return. Biopsy is the definitive diagnostic test for verrucae, but is seldom performed because of the ease and reliability of clinical diagnosis. While the entity is quite frequently encountered, no single therapy has been proven to be universally effective. A review of the literature showed many methods that have been used to treat verrucae (Table I). Although some effectiveness is seen in all of the treatments reviewed in the literature, there is a lack of consensus regarding the most effective and safe treatment. Many factors come into play when determining the most favorable treatment regimen. These include effectiveness of treatment, recurrence rate, length of treatment, cost of treatment, and discomfort to the patient. In 1967, Block (6) stated that ultrasound could effectively be used to treat verrucae plantaris. Ultrasound was applied at an intensity of 0.5 W/cm 2 for 8 minutes to the wart. He reported a cure rate of 88.2% with 15 of 17 warts resolved. This method averaged 9.3 treatments for verrucae, and 19.3 treatments for mosaic warts (6). Most of the cases in this study decreased with ultrasound, but required mechanical debridement or electrocautery for full resolution. Immunotherapy was recommended by Lawrence (3). He felt that no universal treatment had been found to cure warts, and that the immune system could be used to eradicate the verrucae. This concept was predicated upon stimulation of the immune system against the virus. He used the smallpox vaccine, which was carefully monitored

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TABLE 1 Comparison of verruca treatments


Method Number of Warts Reso lved 58 15 Tota l Number of Warts 65 Percentage Resolved (%) Mean Treatm ent Time (weeks) 7.6 Not reported Average Application of Treatment 4.05 of Verruca Freeze 9.3

Verruca-free ze/70 % salicylic Acid Block (1967), ultrasound application Lawrence (1971) , smallpox vaccine Limmer (1979), liq uid nitrogen Grayson (1982), topical ONCS Sullivan (1984), topical corticosteroid Apfelberg (1984), carbon dioxide laser Mahoney (1996), oral cimetidine Borovoy (1996), pulse-dye laser Jacobsen (1997), pulse-dye laser

89.2 88.2

17

107 81 6 16

160 89 10 20

67 91 60 80

Not report ed Not reported Not reported Not reported

Not reported 1.9 Not reported Not reported

33

46

72

Not reported

Not reported

14 159 Not reported

25 200 Not reported

56 79.9 47 (nonrecalcitrant) 68 (recalcitrant)

2.5 - 4.5 Not reported Not reported

Not reported Not reported Not reported

for adverse reac tions. In 160 patients tested, a clinical cure was observed in 67 % of patients (3). In 1979, Limmer indicated that cryosurgery was an effec tive method for wart removal. He used a ha ndheld cryosurgery instrument con taining liquid nitrogen. It was cho sen over other refrigerants such as liquid air, carbon dioxide, and nitrous oxide due to its stable nature, inflammability, low cost, availability, and low temp erature (- 195.6C) (7). Because of the extremely low temperature of the liquid nitro gen, the patient was anestheti zed with a posterior tibial ner ve block. In 89 plantar warts in 40 patients, a 91% cure rate was found. The average follow-up time was 17.5 months, and the mean length of treatment was 1.9 months (7). In 1982, Grayson et al. presented a method using topica l dinitrochIorobenzene (DNCB) therapy to treat verrucae (8). DNCB utilizes the body' s immunologic response by acting as an irritant. The patient is sensitized to DNCB , then a cont rolled hypersensitivity response is used to eradica te the wart. These authors believed that suc h a hypersensitivity reacti on wo uld be observe d in 85-95% of the population (8). In this treat me nt protocol, the DNCB is applied to the medial arm, and a reacti ve derm atitis occ urs within the first 24 hours. Afte r sensitiza tion, the patient applies DNCB to the affec ted area. Approximately 2-3 weeks later, a similar reac tion is observed on the foot where DNCB was applied. The study was performed only on recalcitrant verru cae that had been pre sent for grea ter

than 6 month s. They found that 6 of 10 patients were cured by 0.15 mL of 0.3% DNCB in acet one (8). One potential complication to DNCB is its mutageni c potential. Trea tment with topical corticos teroids under occl usion was reco mmended by Sullivan (2). He believed that topical corticosteroids would be effective because the corticosteroid would lower the growth rate of the cells by slowing cell division and synthesis of DNA in the epidermis (2). The treatment involved applying corti sone tape to the skin ju st after paring the wart to induce pinp oint bleeding. Sixtee n of 20 patients were cured, for an 80% cure rate. No adverse reactions were reported, but skin changes and skin atrophy were cited as possible side eff ects (2). The use of carbon dioxide laser to treat warts was reported by Apfe lberg et al. in 1984 (9). Laser surgery was recommended due to the accura cy of the laser' s foca l spot and its hemostatic properties. In Apfe lberg et al.'s study, 33 of 46 lesions healed - a 72 % success rate. Of 27 solitary verrucae , 26 or 96% healed. Of 16 multiple or mosaic warts, 9 or 56% healed . Sixtyone percent of patients reported mild pain , while only 35% reported no pain (9). The study showed that patients requ ired an average of 2.6 days to return to comfortable walking , and 13 days for complete healin g (9). Further adva ntages were outlined by Goldfarb ( 10), who stated that laser surgery was less painful, and one could reg ulate the depth and diameter of the involved area. Drawback s
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to laser therapy include to be a moderate recurrence rate, special safety concerns, and cost. Lemont recommended blunt dissection to the level of the superficial fascia. Instead of sharp dissection, he used blunt dissection to "pop" the wart out. Lemont believed that removal of skin to the superficial fascia would significantly decrease recurrence rate of treated warts (11). Oral cimetidine was proposed as a treatment for verrucae in 1996. It is believed that the immune response to HPV is cell-mediated. The action of cimetidine on the H2 receptor on the lymphocyte suppressor T-cell would increase the body's cell-mediated immune response to heighten the response against the virus (4). Twenty-four patients were treated for verrucae with oral cimetidine 900-1,800 mg/day. Twelve of 15 patients, or 80%, in the 6- to 17-year-old age group resolved, but in the 17- to 50-year-old population, only 2 of 10 resolved. Length of treatment was between 2.5 and 4.5 weeks. Side effects of nausea, vomiting, and diarrhea were reported (4). However, the FDA has not yet approved the use of oral cimetidine on verrucae (12). Recently, the pulse-dye laser has been introduced as an approach to treating verrucae. This method involves the use of a candela vascular laser to destroy blood vessels that supply the wart. This treatment is considered relatively painless, with the sensation of treatment compared to being snapped by a rubber band (13). In 1997, Jacobsen et al. found that 68% of recalcitrant warts cleared with the pulse-dye laser, but that only 47% not previously treated resolved (13). In 1996, Borovoy (14) also did a study on the pulse-dye laser and found a 79.9 % success rate in recalcitrant warts. One must use good judgment with verrucae, selecting a treatment regimen that is successful, low risk, and as painless as possible. The authors present a treatment method of cryotherapy and 70% salicylic acid. The authors believe this study to be significant because there are no reports in the literature concerning this combined treatment regimen.
Methods

had to exhibit all of the following criteria: interrupted skin lines, pinpoint bleeding, and pain on lateral squeezing of lesion. Fifteen patients were female and 14 were male. The age of patients ranged from 4 years to 51 years old (see Table 2). The median age was 12, and the mean age was 18.9 years old. Patients had from one to six warts, with an average of 2.07 warts per individual. Following debridement, Verruca Freeze was applied for 90 seconds, or to patient's tolerance. Seventy percent salicylic acid was then applied under occlusion. Most over-the-counter salicylic acid preparations are 17%. The 70% salicylic acid is not available in most formularies, but can be compounded by a local pharmacist. The patient was instructed to repeat this acid application nightly for a week and then return for re-evaluation. At each visit salicylic acid was applied. Clinical judgment was used to determine the necessity of weekly Verruca Freeze application. Proximity of verruca eradication, tenderness of area, and the presence of bulla were considered in determination of the necessity for application. Clinical cure was considered when there was return of normal dermatoglyphic skin lines.
Results

A retrospective study was conducted on a patient population from a suburban private practice outside of a large metropolitan area. The charts of patients treated for verruca plantaris from 1992 to 1997 were reviewed. Twenty-nine patients, comprising 65 warts, were treated with a combination of liquid cryotherapy with Verruca Freeze.' and daily topical application of 70% salicylic acid. Verruca Freeze is composed of chlorodifluoromethane and freezes at -70C. To be included in the study the patient
3 Cryosurgery,

Of the 29 patients who underwent this treatment, 25 of them had all of their warts completely resolved based on the return of normal skin lines. This represents 86.2% of patients treated. One patient had only two of the four lesions resolve. Out of 65 warts treated, 58 of those resolved on these 29 individuals; 89.2% of the warts treated using this combined Verruca Freeze/70% salicylic acid treatment were eradicated. Thirty-two of 36 verrucae (88.9%) in the 0- to 12-year-old group resolved. All 10 (100%) of the verrucae in the 13- to 19-year-old group resolved. In the 20- to 55-year-old age bracket, 17 of 19 warts resolved (89.5%). The mean treatment time to eradication was 7.6 weeks. The range of time was 1-32 weeks. Patients receiving treatment required an average of 4.05 applications of the Verruca Freeze. Cryotherapy treatment ranged from 1 to 18 treatments. Patient follow-up averaged 2.9 years.
Discussion

Inc., Nashville, TN.

In this retrospective study of 65 warts treated by Verruca Freezel70% salicylic acid, several interesting points were discovered. First, the success rate of the combined cryotherapy/70% salicylic acid was higher than all other methods in the literature, with exception of the liquid nitrogen. However, this method requires anesthesia to administer.

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TABLE 2 Sex

Analysis of Verruca Freezel70% salicylic acid treatment Age Weeks to Hesolution Number of Office Visits In-office Applications of 70% Salicylic Acid 4 17 3 3 3 3 3 3 7 7 7 15 20 3 3 3 3 3 11 7 7 5 5 5 3 3 3 6 6 8 12 2 2 8 8 8 1 1 4 3 10 10 10 9 9 4 4 2 2 2 4 4 16 3 16 In-office Applications of Verruca Freeze Length of Follow-up (years)

F M M M M M M M M M M M M F F F F F M F F F F F M M M F F M M M M F F F F F F M M M M M F F F M M F M F M M M

10 11 7 7 7 7 7 7 15 15 15 15 15 12 12 12 12 12 8 8 8 6 6 6 51 51 51 11 11 36 20 25 25 44 44 44 15 15 15 39 39 39 39 6 8 50 50 47 4 12 14 12 10 10 10

4 20 3 3 3 3 3 4.5 8 8 8 16 20 3 2 2 7 7 16 8 8 6 6 6 3 3 3 Unresolved Unresolved 11 16 8 8 10 10 10 2 2 12 12 12 Unresolved Unresolved 9 9 6 6 Unresolved 2 2 4 4 32 3 18

4 17 3 3 3 3 3 4 7 7 7 15 20 3 3 3 3 3 11 7 7 5 5 5 3 3 3 6 6 8 12 2 2 8 8 8 1 1 4 3 10 10 10 9 9 4 4 2 2 2 4 4 16 3 16

2 8 1 1 1 1 1 2 6 6 6 11 15 1 2 2 7 7 10 4 4 3 3 3 2 2 2

1.5 2 2.75 2.75 2.75 2.75 2.75 2.75 3 3 3 3 3 2.5 2.5 2.5 2.5 2.5 3.5 4.5 4.5 5 5 5 1.5 1.5 1.5

5 9 2 2 7 7 7 1 1 4 3 3

8 5 4 4 3 2 4 3 10 1 3

2.25 2.5 2 2 2 2 2 3.75 3.75 3.75 3 3 3 3 3 3.5 2.5 2.5 1 2 3 4.5 4.5 4.5 4.5

(continued)

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TABLE 2

(Continued) Age Weeks to Resolution Number of Office Visits In-office Applications of 70% Salicylic Acid In-office Applications of Verruca Freeze Length of Follow-up (years)

Sex

F F F F F F F F F F

8 8 12 12 12 12 12 31 31 15

Unresolved Unresolved

2 2 2 12 12 3 7 9

6 6 1 1 1 4 4 3 6 8

6 6
1 1 1 1 1

1 4 4 3 6 8

5 5
1

2 8

2.5 2.5 2.5 2.5 2.5 2.5 2.5 3.75

Each row represents one verruca

Second, the combined cryotherapy/70% salicylic acid therapy was more successful than the carbon dioxide laser surgery. The combined treatment cure rate was 89.2%, whereas Apfelberg et al. reported a 72% overall cure rate with the carbon dioxide laser. Although the treatment time averaged 7.6 weeks for the combined salicylic acidlVerruca Freeze method, the treatment does not disrupt the patients' lifestyle (walking, running, working, showering). The third key point from our study compares our proposed combined therapy to Limmer's study, which also used cryotherapy. They found a 91% cure rate with a mean treatment time of 1.9 cryotherapy doses. The combined Verruca Freeze/70% salicylic acid treatment cured 89.2% of warts, but required an average of 4.05 cryotherapy applications. Limmer had to use local anesthesia in order to give patients the liquid nitrogen treatment. The liquid nitrogen used by Limmer has a much lower freezing point, -195.6C, than the Verruca Freeze, which freezes at -70C. Hence the combined Verruca Freeze/70 % salicylic acid treatment does not require any local anesthesia. In Limmer's method, the patient is subjected to some risk from the local anesthetic, but more notably the pain from the injection, and a deeper cryoburn. In the authors' opinion, patients have reacted favorably to this combined treatment scheme because it does not involve injections, and is not invasive. The use of the 70% salicylic acid with cryotherapy allows for a gentler, yet highly effective and efficient treatment. In this study with the cryotherapy/70% salicylic acid treatment, one concern might be self-administration of the highly concentrated salicylic acid. Patients were seen weekly and during the course of their treatment no adverse effects were reported in their medical records. The authors believe that with adequate patient education, the patient can successfully, easily, and consistently apply
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the nightly dose of 70% salicylic acid without adverse results.

Conclusion

The combined Verucca Freeze/70% salicylic acid treatment method outlined in this article is recommended as a gentle, efficient, low-risk, and highly successful method to treat verrucae. Of the 65 treated warts, 89.2% resolved successfully via this method over an average of 7.6 weeks and 4.05 cryogen applications. The results are quite successful when compared to other conservative and surgical methods of verruca removal.

Acknowledgments Special thanks to Annamary Rymann for her technical support with the research involved in this study.
References
1. Fitzpatrick, T. B., Johnson, R A., Wolff, K, Polano, M. K., Suurmond, D. Human papillomavirus infections, ch. 28. In Color Atlas and Synopsis of Clinical Dermatology, 3rd ed., pp. 766- 768, McGraw-Hill, New York, 1997. 2. Sullivan, T. M. Treatment of resistant warts with topical corticosteroids and occlusion. 1. Am. Podiatr. Assoc. 74(3):141-143,1984. 3. Lawrence, K. R Treatment of verrucae with smallpox vaccine. J. Am. Podiatr. Assoc. 61(1):12-19,1971. 4. Mahoney, J. M. Oral cimetidine and the treatment of verrucae. J. Am. Podiatr. Med. Assoc. 86(4):183-186, 1996. 5. Lewis, M. R, Lutterbeck, E. F. Verrucae: a clinical review. 1. Am. Podiatr. Assoc. 57(6):263-268, 1967. 6. Block, D. Treatment of verruca plantaris with ultrasound. J. Am. Podiatr. Assoc. 57(7):327-328, 1967. 7. Limmer, B. L., Bogy, L. T. Cryosurgery of plantar warts. J. Am. Podiatr. Assoc. 69(12):713-716, 1979.

8. Grayson, R. J., Ratner , S. W., Shaps, R. S. Topical DNCB therapy for recal citrant verruca plantari s. J. Am. Podiatr. Assoc. 72(lI ): 557 -559, 1982. 9. Apfelberg , D. B., Rothermel , E., Widtfeldt , A., Maser , M. R., Lash , H. Preliminary report on use of carbon dioxide laser in podiatry. J. Am. Podiatr. Assoc. 74(10):509- 5 13, 1984. 10. Goldfarb, M. T., Gupta, A. K.. Gupta , M. A., Sawchuk, W. S. Office therapy for human papillomavirus infection in nongenital sites. Dermatol . Clin. 9(2):287 - 296, 1991. II. Lemont , H., Parekh, V. Superficial fascia: an appropriate anatomical boundary for excising warts on the foot. 1. Am. Podiatr. Med. Assoc. 83(10):598-599, 1993. 12. Dubov, S. F. Verrucae. Podiatr . Mgmt., Sept. , 1998 . 13. Jacob sen, E., McGraw , R., McCagh, S. Pulsed dye laser efficacy as initial therapy for warts and against recalcitrant verrucae. Cutis 59:206 -208, 1997. 14. Borovoy , M. A., Borovoy , M., Elson, L. M., Sage, M. Flashl amp pulsed dye laser (585 nm): treatment of resistant verrucae. J. Am. Podiatr. Med. Assoc. 86(11) :547 -551 , 1996.

Suggested Reading
Hochhauser, D. HPV predicts poorer prognosis in early-stage cerv ical cancer. Lancet 348:1088, 1996. Iwasaka, T. Non-dete ction of DNA in cervical dysplasia and progression to invasive carcinoma. Lancet 348 :333, 1996 . Luciano, C. S. Verruca plantaris: a compendium of its understanding and treatment. 1. Am. Podiatr. Assoc. 67(12 ):858-870, 1977. McCarth y, D. 1. A morphog enic and histochemical analysis of pressure prone verrucae of the human foot. J. Am. Podiatr. Assoc. 67(6):377 - 388, 1977. McCarthy, D. J., Tate, R., Rusin, J., Intradermal use of 5-fluorouracil in human pedal verrucae. J. Am. Podiatr . Assoc. 69(10):587-598, 1979 . Rosenthal , A. N., Ryan, A. p53 codon 72 polymorphism and risk of cervical cancer in UK. Lancet 352:87 1- 872, 1998. Suppan, R. 1., Besterman, G. Curett age and chemotherapy for verrucae. 1. Am. Podiatr. Assoc. 53(4):265-268, 1963.

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