Imiquimod

Abstract

Treatment of plantar warts is often difficult and may be painful, often employing destructive treatment modalities. We report the successful treatment of a patient with a large plantar wart using Imiquimod 5% cream under occlusion with a 40% salicylic acid pad. This combination treatment modality likely allows successful delivery of Imiquimod through the thick skin on the plantar surface. Once penetrated, an anti-viral state is created by upregulating specific cytokines to eradicate the human papilloma virus (HPV).

Background

Plantar warts are known to be difficult to treat and eradicate. They are caused by a proliferation of human papilloma virus (HPV) on the plantar surfaces of the feet; the most common serotype is HPV 1 (1). Conventional treatment strategies are often destructive in nature. These treatment modalities work by destroying the keratinocytes infected by HPV; however, replication of the virus is not affected. The methods of treatment that are described in the literature include cryotherapy, electrodessication, carbon dioxide laser ablation, and simple paring of thick plantar lesions (2). Other known plantar wart therapies include intralesional Bleomycin (3), application of topical podophyllin, and cantharidin (4), and the use of topical salicylic acid.

More recent efforts have focused on inhibiting HPV replication. Intralesional injection of interferon alfa (IFN-a) has been shown to be effective in the treatment of genital warts (5). This type of treatment has several downfalls: it requires multiple intralesional injections, it is poorly absorbed, and there is a high recurrence rate after treatment. More recently, Imiquimod 5% cream, an immune response modifier, has been shown to be effective in the treatment of genital warts. Imiquimod induces the production of IFN-a, interleukins (IL) 1, 6, and 8, IL-1 receptor antagonist, and rumor necrosis factor (TNF)-a (6,7). It is believed that induction of these immunologic mediators will result in virus inhibition and eradication as opposed to mere keratinocyte destruction. The immune-enhancing effect of Imiquimod will likely extend to the treatment of many any other dermatologic conditions. The use of Imiquimod in the treatment of superficial basal cell carcinomas has been described recently (8).

Case Report

A 38 year-old Caucasian male presented to our clinic in July 1999 with a 3.0 x 2.0 cm painful, verrucous (mosaic-type) lesion on his left plantar foot present for the past year (Figure A). He stated that his only other medical condition is a heart murmur for which he takes enalapril daily. He denied any known infectious disease or state of immunosuppression.

[FIGURE A OMITTED]

Over the preceding year, the patient received numerous treatment modalities including over-the-counter acid pads as well as numerous therapies via outside dermatologist. We began treatment with cryotherapy and paring, which showed minimal improvement after one month (Figure B). Over the following six months, attempts at appeared to have resolved completely. Only a nontender scar remained on the plantar surface (Figure D).

[FIGURES B & D OMITTED]

Discussion

The treatment of cutaneous diseases with immune-modifying agents is not a new modality, but has been expanded recently through new formulations. Also, inclusion of a wider range of diseases that may benefit from such treatment have emerged. Imiquimod, an immune modulator, has been approved for the use of genital warts. In this case study, the cream was used on the plantar surface of the foot. Since plantar warts have an extremely thick keratinization pattern, transepidermal delivery of topical agents, such as Imiquimod, may be impaired.

A recent case report of plantar wart treatment with topical Imiquimod showed no benefit with application nightly three times per week without occlusion. However, application of liquid nitrogen to lesions followed by nightly application of Imiquimod under duct-tape occlusion resulted in resolution within 12 weeks (9).

Weakening of the stratum corneum by methods such as cryotherapy or the use of occlusive acid pads may be necessary for adequate Imiquimod penetration into plantar warts. Our combined use of Imiquimod under salicylic acid pad occlusion represents a convenient and easy way to treat recalcitrant plantar warts at home, avoiding more painful options such as cryotherapy or laser therapy and decreasing the frequency of office visits.

We have now successfully used this combination therapy on several patients with plantar warts. The use of Imiquimod 5% cream, an immune modulator, along with traditional destructive modalities, provides the physician with an increased armamentarium to treat plantar warts.

[FIGURE C OMITTED]

References

(1) Lowy DR and Androphy EJ. Warts. In: Fitzpatrick's Dermatology in General Medicine. 5th Edition. Mc-Graw Hill; New York. Ch. 56. pp. 2484-2497.

(2) Pringle WM and Helms DC. Treatment of plantar warts by blunt dissection. Arch Dermatol 1973; 108(1):79-82.

(3) Shumer SM, and O'Keefe EJ. Bleomycin in the treatment of recalcitrant warts. J Am Acad Dermatol 1983; 9(1):91-96.

(4) Coskey RJ. Treatment of plantar warts in children with a salicylic acid-podophyllin-cantharidin product. Pediatr Dermatol 1984; 2(1):71-3.

(5) Eron LJ, Judson F, and Tucker S. Interferon therapy for condylomata acuminata. N Engl J Med 1986; 315:1059-1064.

(6) Megyeri K, Au WC, Rosztoczy I, et al. Stimulation of interferon and cytokine gene expression by imiquimod and stimulation by Sendai virus utilize similar signal transduction pathways. Mol Cell Biol 1995; 15:2207-2218.

(7) Testerman TL, Gerster JF, Imbertson LM, et al. Cytokine induction by the immunomodulators imiquimod and S-27609. J Leukoc Biol 1995; 58:365-372.

(8) Drehs MM, Cook-Bolden F, Tanzi EL, and Weinberg, JM. Successful treatment of multiple superficial basal cell carcinomas with topical imiquimod: case report and review of the literature. Derm Surgery 2002; 28(5):427-9.

(9) Sparling JD, Checketts SR, and Chapman MS. Imiquimod for plantar and periungual warts. Cutis 2001; 68(6):397-399.

ADDRESS FOR CORRESPONDENCE:

Asra Ali M.D.

Department of Dermatology,

University of Texas-Houston Medical School

6431 Fannin, Suite 1.204

Houston, TX 77030, USA

Phone: 713-500-7865 * Fax: 713-500-7168

STEPHEN B. TUCKER MD (1), ASRA ALI MD (2), BRIAN L. RANSDELL, BA (3)

(1.) CLINICAL PROFESSOR, DEPARTMENT OF DERMATOLOGY, UNIVERSITY OF TEXAS-HOUSTON MEDICAL SCHOOL, HOUSTON, TEXAS. (2.) ASSISTANT PROFESSOR, DEPARTMENT OF DERMATOLOGY, UNIVERSITY OF TEXAS-HOUSTON MEDICAL SCHOOL, HOUSTON, TEXAS. (3.) MEDICAL STUDENT, BAYLOR COLLEGE OF MEDICINE, HOUSTON, TEXAS.

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