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Table of Contents 
Year : 2015  |  Volume : 60  |  Issue : 1  |  Page : 102
Topical adapalene in the treatment of plantar warts; Randomized comparative open trial in comparison with cryo-therapy

1 Department of Dermatology, Indraprastha Apollo Hospital, Sarita Vihar, New Delhi, India
2 Department of Rheumatology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Health, Bethesda, Maryland, USA

Date of Web Publication26-Dec-2014

Correspondence Address:
Ramji Gupta
M-54, Jal Vihar Road, Lajpat Nagar-II, New Delhi - 110 024
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-5154.147835

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Background: Various therapeutic modalities, which are available for treating plantar wart, have not been successful every time. Aims: To evaluate topical adapalene under occlusion in the treatment of plantar warts and compare it with cryo-therapy. Materials and Methods: 50 patients with 424 plantar warts were included in this single center, two arm, prospective, randomized, control, open study. Patients were allocated randomly into two groups consisting of 25 patients each. Group A patients having 299 plantar warts were treated using adapalene gel 0.1% under occlusion while Group B patients having 125 warts were treated using cryo-therapy. All the patients were evaluated weekly till the clearance of all the warts and the results compared. Result: All the warts of 25 patients of Group A that were treated using adapalene gel 0.1% cleared in 36.71 ± 19.24 (55.95-17.47) days except those in one patient. In Group B, warts in all except one treated by cryo-therapy cleared in 52.17 ± 30.06 (82.23-22.11) days. There were no side effects like scar formation, irritation, erythema, or infections with adapalene group while in the cryo group scar was seen in 2 patients, pain in 24, erythema in 10, and infection in 3 patients. Conclusion: Adapalene gel 0.1% under occlusion is an effective, safe and easy to use treatment for plantar warts and may help clear lesions faster than cryo-therapy.

Keywords: Adapalene, cryo-therapy, occlusion, plantar wart

How to cite this article:
Gupta R, Gupta S. Topical adapalene in the treatment of plantar warts; Randomized comparative open trial in comparison with cryo-therapy. Indian J Dermatol 2015;60:102

How to cite this URL:
Gupta R, Gupta S. Topical adapalene in the treatment of plantar warts; Randomized comparative open trial in comparison with cryo-therapy. Indian J Dermatol [serial online] 2015 [cited 2020 Sep 26];60:102. Available from: http://www.e-ijd.org/text.asp?2015/60/1/102/147835

What was known?
Treatment result of plantar warts is not uniform.

   Introduction Top

Treatment of plantar warts, which are caused by human papilloma virus (HPV) type 1, 2, and 4, is often challenging. Various therapeutic modalities that have been used for treating it have not been successful every time. [1],[2],[3],[4]

Adapalene, a synthetic naphthoic acid derivative, is very commonly used in the treatment of mild-to-moderate acne. [5],[6] It is available as 0.1% aqueous gel. It is a retinoid with ability to alter keratinization and affinity for retinoic acid receptor (RARY). [7] It is found predominantly in the epidermis. It has been found to have anti-inflammatory action, inhibits cell proliferation, and modulates cell differentiation. [8],[9] After successful treatment of 10 patients with a total 118 warts, with topical adapalene 0.1% gel, with occlusion, [10] subsequently we studied it in a larger number of patients in a prospective, randomized, control, open trial in comparison with cryo therapy. Data on 50 patients were randomly allocated into two groups, one group was treated with 0.1% adapalene gel under occlusion and the other group with cryo-therapy [11] are presented. Time taken to complete clearance of lesions was compared between the two groups.

   Materials and Methods Top

Fifty patients with 424 plantar warts were included in this single center, two arm, prospective, randomized, control, and open study. Diagnosis of plantar warts was made based on clinical presentation like rough surface, well-defined border [Figure 1] and pain on pressure. Informed consent was taken from all the patients after explaining in details about the purpose and procedure of the treatment. Healthy patients with plantar warts were included in the study. Those patients who were on any systemic therapy in the past 8 weeks and pregnant women were excluded from the study. All topical treatment was stopped 4 weeks prior to the study. Patients were randomly allocated into two treatment groups: Group A (Adapalene 0.1% gel) and Group B (cryo- therapy, very commonly used therapy for plantar warts in this part of country). Comparison was not done with placebo due to fear that many patients may drop during follow-up due to ineffectiveness. All the odd numbered patients, who came to the outpatient department, were allocated to Group A, while all the even numbered patients were allocated to Group B. Thus, 25 patients who were allocated to Group A were treated with topical adapalene 0.1% gel applied twice daily under occlusion using plastic wrap while another 25 patients who were allocated to Group B were treated with cryo-therapy for1-2 minutes using N 2 O gas operated machine with -94°C temperature. Cryo-therapy was repeated within 2 weeks, if there were no signs of improvements in the form of reduction in the pain and/or development of black spots. Once there was improvement, they were followed up for clearance without any cryo sitting. In both the groups, hyperkeratosis or thick areas were pared before doing cryo-therapy or applying adapalene gel. Thus paring was done initially during treatment. The treatment was continued till the clearance of all the warts [Figure 2] in both the groups. The effect of treatment was evaluated weekly till the clearance of all the warts, followed by monthly evaluation for at least 6 months for any recurrences.
Figure 1: Plantar warts before treatment

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Figure 2: Plantar warts after treatment

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Statistical analysis

A test of significance using Student's t-test was employed to see the efficacy of both the treatments in terms of duration of clearance of warts. At 9 degrees of freedom and 5% level of significance it was found that there was a significant difference between both treatment regimes. On the basis of limited data, it was found that use of treatment regime of adapalene (0.1%) with occlusion has reduced duration of clearance of warts in these patients (P < 0.05).

   Results Top

Fifty patients (M-26, F-24) with 424 warts were enrolled in this study. The mean age of all the patients was 27.56 (13-55) years and the mean duration of the warts was 8.31 months. One patient in each group was lost to follow-up. In Group A, all the warts in 24 patients disappeared in 36.71 ± 19.24 days [Table 1]. In Group B, all the warts in 24 patients disappeared in 52.17 ± 30.06 days [Table 2] in an average of 1.88 (1-4) sittings of cryo-therapy.
Table 1: Detail of patients treated by adapalene gel 0.1% under occlusion

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Table 2: Detail of patients treated by cryo-therapy

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There was no recurrence in any patient followed up for an average of 8.47 months.

On comparison of each group [Table 3], patients in Group A, treated with adapalene with occlusion, achieved complete clearance of their lesions sooner than patients in Group B, treated with cryo-therapy.
Table 3: Comparison of treatment by adapalene gel 0.1% and cryo-therapy

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Side effects

There was no side effect like irritation, erythema, infection, or scar formation in any patient treated by adapalene gel. However, patients of the cryo group developed scar in 2 patients, pain in all 24 patients, erythema in 10 patients, and infection in 3 patients.

   Discussion Top

Various immuno-modulating agents used for treatments of warts include oral cimetidine and levamisole, [12],[13] intralesional BCG vaccines, interferon, and imiquimod. [14],[15],[16] The aim of using immuno-therapy is to hasten the clearance of warts although the mechanism is still not clear. One theory suggests induction of a type IV hypersensitivity reaction another suggesting that the substance acts as a hapten to wart virus proteins to induce an immune reaction to HPV.

In a comparative study by Parsad et al. [13] oral cimetidine was able to clear lesions in 11 weeks in 31.5% of cases only where as cimetidine + levamisole took 7.8 weeks. Imiquimod, another immuno-modulator, was reported to clear the plantar warts when used with occlusion in 12 weeks. [14] Gelmetti et al. [17] used etretinate 1 mg/kg/day orally, in 20 children, for 3 months with extensive warts. Sixteen children showed complete regression, without relapse, while in 4, lesions relapsed after initial regression. Choi et al. [18] used acitretin 0.5 mg/kg body weight/day orally for 3 months in an extensive and recalcitrant wart with complete clearance of the lesion. Euvrard et al. [19] were the first to use topical retinoid in warts, in a transplant recipient patient, with good result.

In the present study, use of topical adapalene aqueous gel 0.1% under occlusion resulted in complete clearance of 286 plantar warts in 24 patients in 36.71 ± 19.24 days while 124 warts in 24 patients treated with cryo-therapy took 52.17 ± 30.06 days (P < 0.05). Thus adapalene gel 0.1% under occlusion is more effective than cryo-therapy in the treatment of plantar warts. There are several advantages of using adapalene over cryo-therapy. Adapalene, besides clearing the warts fast, also has no side effects. It is simple and convenient to apply.

In conclusion, topical adapalene under occlusion seems to be an effective, simple, and convenient to apply and safe modality of therapy for treatment of plantar warts and may help clear wart lesions sooner when compared to cryo-therapy. However, with topical adapalene, the patient has to use plastic occlusion daily which may be messy and may not be liked by some patients. It also needs confirmation by further study by more workers as it is the first study of its kind.

   Acknowledgement Top

The author thanks Mr. Anil Gupta, Center for Social Medicine and Community Health, Jawaharlal Nehru University, New Delhi, India for statistical assistance.

   References Top

Gibbs S, Harvey I, Sterling J, Stark R. Local treatments for cutaneous warts: Systematic review. BMJ 2002;325:461.  Back to cited text no. 1
Bacelieri R, Johnson SM. Cutaneous warts: An evidence-based approach to therapy. Am Fam Physician 2005;72:647-52.  Back to cited text no. 2
Sterling JC, Handfield-Jones S, Hudson PM; Guidelines for the management of cutaneous warts. Br J Dermatol 2001;144:4-11.  Back to cited text no. 3
Kwok CS, Gibbs S, Bennett C, Holland R, Abbott R. Topical treatments for cutaneous warts. Cochrane Database Syst Rev 2012;9:CD001781.  Back to cited text no. 4
Brogden RN, Goa KE. Adapalene. A review of its pharmacological properties and clinical potential in the management of mild to moderate acne. Drugs 1997;53:511-9.  Back to cited text no. 5
Shalita A, Weiss JS, Chalker DK, Ellis CN, Greenspan A, Katz HI, et al. A comparison of the efficacy and safety of adapalene gel 0.1% and tretinoin gel 0.025% in the treatment of acne vulgaris: A multicenter trial. J Am Acad Dermatol 1996;34:482-5.  Back to cited text no. 6
Bernard BA. Adapalene, a new chemical entity with retinoid activity. Skin Pharmacol 1993;6 Suppl 1:61-9.  Back to cited text no. 7
Hensby C, Cavey D, Bouclier M, chatelus A, Algate D, Eustache J, et al. The in vivo and in vitro anti-inflammatory activity of CD271: A new retinoid-like modulator of cell differentiation. Agents Actions 1990;29:56-8.  Back to cited text no. 8
Asselineau D, Cavey MT, Shroot B, Darmon M. Control of epidermal differentiation by a retinoid analogue unable to bind to cytosolic retinoic acid-binding proteins (CRABP). J Invest Dermatol 1992;98:128-34.  Back to cited text no. 9
Gupta R. Plantar warts treated with topical adapalene. Indian J Dermatol 2011;56:513-4.  Back to cited text no. 10
[PUBMED]  Medknow Journal  
Limmer BL, Bogy LT. Cryosurgery of plantar warts. J Am Podiatry Assoc 1979;69:713-6.  Back to cited text no. 11
Saul A, Sanz R, Gomez M. Treatment of multiple viral warts with levamisole. Int J Dermatol 1980;19:342-3.  Back to cited text no. 12
Parsad D, Saini R, Negi KS. Comparison of combination of cimetidine and levamisole with cimetidine alone in the treatment of recalcitrant warts. Australas J Dermatol 1999;40:93-5.  Back to cited text no. 13
Tucker SB, Ali A, Ransdell BL. Plantar wart treatment with combination imiquimod and salicylic acid pads. J Drugs Dermatol 2003;2:124-6.  Back to cited text no. 14
Muzio G, Massone C, Rebora A. Treatment of non-genital warts with topical imiquimod 5% cream. Eur J Dermatol 2002;12:347-9.  Back to cited text no. 15
Grussendorf-Conen EI, Jacobs S. Efficacy of imiquimod 5% cream in the treatment of recalcitrant warts in children. Pediatr Dermatol 2002;19:263-6.  Back to cited text no. 16
Gelmetti C, Cerri D, Schiuma AA, Menni S. Treatment of extensive warts with etretinate: A clinical trial in 20 children. Pediatr Dermatol 1987;4:254-8.  Back to cited text no. 17
Choi YL, Lee KJ, Kim WS, lee DY, Lee JH, Lee ES, et al. Treatment of extensive and recalcitrant viral warts with acitretin. Int J Dermatol 2006;45:480-2.  Back to cited text no. 18
Euvrard S, Verschoore M, Touraine JL, Dureau G, Cochat P, Czernielewski J, et al. Topical retinoids for warts and keratoses in transplant recipients. Lancet 1992;340:48-9.  Back to cited text no. 19

What is new?
Adapalene a new compound is able to clear the plantar warts fast without any side effect.


  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3]


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