Laser-Assisted Delivery of Topical Cidofovir in the Treatment of Plantar Warts

The treatment of plantar warts is challenging and current therapies often do not result in satisfactory clearance of verrucae.¹ A large number of plantar warts, particularly those that are large and hyperkeratotic, are recalcitrant to first-line treatments. For instance, cryotherapy and salicylic acid have not demonstrated superiority compared to a wait-and-see approach.²

Numerous therapeutic modalities have been utilized in the treatment of plantar warts, including topical cantharidin-podophyllotoxin-salicylic acid,³ topical trichloroacetic acid,⁴ topical 5% imiquimod,⁵ intralesional mumps, Candida, or Trichophyton antigen,⁶ and intralesional 5-fluorouracil.⁷ Cidofovir, a nucleotide analogue, is a potent inhibitor of viral DNA polymerase but is nephrotoxic when administered systemically.⁸ Local administration of this medication shows significant promise for treating HPV-related verrucous neoplasms. Treatment with intralesional cidofovir has demonstrated complete clearance of plantar warts in up to 98% of patients.⁹ Despite recent advances in therapeutic options for plantar warts, patients with symptomatic, large verrucous nodules and tumors remain a therapeutic challenge.

Ablative fractional lasers (AFLs) can be utilized to facilitate drug delivery beyond the stratum corneum and target lesions located within the deeper epidermis and dermis. This technique, known as laser-assisted drug delivery (LAD), has been utilized for various cutaneous applications in treating actinic keratoses,1⁰ non-melanoma skin cancers,^11,12 and hypertrophic scars.¹³ Several AFLs, including erbium:yttrium-aluminum-garnet (Er:YAG) and carbon dioxide (CO2), are emerging as new treatment options for recalcitrant warts, with clearance rates reported between 47% and 100%.¹⁴ For example, one study showed that treatment with Er:YAG followed by topical podophyllotoxin resulted in complete lesion clearance in 89% of patients with plantar warts.¹⁵ In this report, we describe two cases of refractory plantar verrucae treated with Er:YAG and topical cidofovir.

Patient 1

A 59-year-old male presented with an eight-year history of a gradually enlarging painful verrucous tumor on the right heel that made it difficult to wear closed footwear. A biopsy was consistent with verruca. This lesion had been previously treated with excision, salicylic acid, and cantharidin. He then received three treatments with pulsed dye laser and 40% urea cream; initial improvement was noted, but the lesions exhibited recurrent growth within weeks. A trial of AFL-assisted delivery of topical cidofovir 75mg/mL was proposed. Pre-treatment examination demonstrated a 5.5 x 4 cm yellow hyperkeratotic verrucous tumor on the right posterior heel (Figure 1A). Treatment was initiated with a 2940-nm Er:YAG laser with a 5-mm-spot size, short pulse pattern with a density of 11% and 1.5 mm depth. Following each laser treatment, 1 mL of cidofovir 75mg/mL was applied topically to the treated area and was covered with an occlusive transparent medical dressing for 1 hour (Figure 1B). Following nine serial treatments every two to six weeks, the lesion demonstrated approximately 60% decrease in tumor size with islands of complete clearance and markedly decreased hyperkeratosis; furthermore, the patient was able to resume wearing closed footwear (Figure 1C).