The Use of Imiquimod in the Treatment of Flat Warts

In response to July’s “What’s Your Diagnosis?” article on flat warts (verrucae plana), by Alexander K. C. Leung, MD, and Benjamin Barankin, MD:

There is excellent evidence-based medicine, known since its inception, that imiquimod has absolutely no effect on warts. Even the manufacturer admits that it should only be used on thin-walled warts (molluscum, which are poxvirus warts). Imiquimod deserves to be relegated to the closet of useless treatments along with frogs and stump water.

Robert B. Golenbock, MD

Newtown, Connecticut

The authors respond:

In our article,¹ we mentioned that the 2 most common treatments for flat warts are salicylic acid and cryotherapy with liquid nitrogen. Other treatment options include imiquimod, duct tape, and laser therapy. Each treatment decision must be individualized, taking into consideration efficacy and cost; the experience of the physician; the location, size, and number of lesions; and the patient’s age and treatment preference.

Verrucae, commonly known as warts, are caused by human papillomavirus. Imiquimod, an aminoquinoline compound, works by stimulating local peripheral mononuclear blood cells and keratinocytes to secrete cytokines, including interferon alfa, interferon gamma, tumor necrosis factor α, and interleukins 1, 6, 8, and 12.^2,3 The secreted cytokines stimulate local immune effects that are cytotoxic against human papillomavirus without causing tissue destruction.³ Imiquimod also acts on cell-mediated immunity by activating Langerhans cells, thereby increasing the presentation of antigens for the T cells.⁴

We disagree that imiquimod has absolutely no effects on warts. There is ample scientific evidence that imiquimod is effective and safe in the treatment of anogenital warts,⁵ as well as warts elsewhere in the body.^2,3,6-14

In one open-label clinical trial, 50 patients with 3 to 100 common warts resistant to previous therapies were treated with imiquimod 5% cream once nightly for 5 consecutive nights per week, and the medication was left on overnight and washed off with soap and water the following morning.⁸ Twenty-eight (56%) patients achieved either total clearance (n = 15; 30%) or a greater than 50% reduction in wart size (n = 13; 26%) after a mean treatment period of 9.2 weeks.

In another trial, 18 children with long-lasting (2-7 years) recalcitrant cutaneous warts were treated with imiquimod 5% cream twice daily.⁶ Assessment for response was performed every 4 weeks until clinical cure. Sixteen (89%) patients experienced total clearance of the warts; two (11%) showed partial improvement but were lost to follow-up.

Kim and colleagues treated 15 patients who had flat warts with imiquimod 5% cream applied nightly for 12 weeks.¹⁰ The cream was discontinued when the warts disappeared completely. At 12 weeks, 6 (40%) patients had complete clearance of the lesions, and 5 patients (33%) had an excellent response (76% to 99% clearance).

Imiquimod 5% cream also has been shown to be effective for the treatment of recalcitrant cutaneous warts in immunosuppressed individuals.^7,15 Particularly for sensitive locations on the face, and especially in patients unable to tolerate pain (eg, children), imiquimod remains an important option in our therapeutic armamentarium.

Alexander K. C. Leung, MD, University of Calgary, and Benjamin Barankin, MD, Toronto Dermatology Centre

REFERENCES

1. Leung AKC, Barankin B. Flat, flesh-colored, painless papular lesions around a boy’s mouth: flat warts (verrucae plana). Consult Pediatrician. 2014;13(7):313-315.

2. Dasher DA, Burkhart CN, Morell DS. Immunotherapy for childhood warts. Pediatr Ann. 2009;38(7):373-379.

3. Niiyama S, Amoh Y, Katsuoka K. Successful treatment of verrucae planae with imiquimod 5% cream. Acta Dermatovenerol Croat. 2011;19(4):273-274.

4. Brandt HRC, Fernandes JD, Patriota RGC, Criado PR, Belda Junior W. Treatment of human papillomavirus in childhood with imiquimod 5% cream. An Bras Dermatol. 2010;85(4):549-553.

5. Baker DA, Ferris DG, Martens MG, et al. Imiquimod 3.75% cream applied daily to treat anogenital warts: combined results from women in two randomized, placebo-controlled studies. Infect Dis Obstet Gynecol. 2011;2011:806105. doi:10.1155/2011/806105.

6. Grussendorf-Conen E-I, Jacobs S. Efficacy of imiquimod 5% cream in the treatment of recalcitrant warts in children. Pediatr Dermatol. 2002;19(3):263-266.

7. Harwood CA, Perrett CM, Brown VL, Leigh IM, McGregor JM, Proby CM. Imiquimod cream 5% for recalcitrant cutaneous warts in immunosuppressed individuals. Br J Dermatol. 2005;152(1):122-129.

8. Hengge UR, Esser S, Schultewolter T, et al. Self-administered topical 5% imiquimod for the treatment of common warts and molluscum contagiosum. Br J Dermatol. 2000;143(5):1026-1031.

9. Khan Durani B, Jappe U. Successful treatment of facial plane warts with imiquimod. Br J Dermatol. 2002;147(5):1018.

10. Kim M-B, Ko H-C, Jang H-S, Oh C-K, Kwon K-S. Treatment of flat wars with 5% imiquimod cream. J Eur Acad Dermatol Venereol. 2006;20(10):1349-1350.

11. López-Giménez MT. Five cases of recalcitrant plantar warts successfully treated with imiquimod 5% cream. Actas Dermosifiliogr. 2013;104(7):640-642.

12. Mühlstädt M, Kerschenlohr K, Scharrer E-M, Pfützner W, Korting HC. Juvenile verrucae planae: treatment with imiquimod 5% cream [in German]. Hautarzt. 2007;58(1):54-55.

13. Oster-Schmidt C. Imiquimod: a new possibility for treatment-resistant verrucae planae. Arch Dermatol. 2001;137(5):666-667. 

14. Schwab RA, Elston DM. Topical imiquimod for recalcitrant facial flat warts. Cutis. 2000;65(3):160-162.

15. Walzman M. Successful treatment of profuse recalcitrant extra-genital warts in an HIV-positive patient using 5% imiquimod cream. Int J STD AID. 2009;20(9):657-658.