Skin Therapy Letter Hydrogen Peroxide Topical Solution, 40% (w/w) for the Treatment of Seborrheic Keratoses A Review Emily C. Murphy, BS; Adam J. Friedman, MD DISCLOSURES Skin Therapy Letter. 2020;25(1):1-4. Abstract and Introduction Abstract HP40 (Eskata™) is a stabilized, topical solution of 40% hydrogen peroxide (H2O2) packaged in an applicator pen that is US FDA-approved to treat seborrheic keratoses (SKs). By harnessing the oxidative capabilities of H2O2 , 1–2 treatments with HP40 produced a higher rate of clearance of four SKs per patient compared to vehicle in two phase 3 trials. The clearance rate was higher for the face than the trunk and extremities. Similarly, the risks of pigmentary changes and scarring from HP40 were lower for the face than other locations. Further, based on an ex vivo study, HP40 may be less cytotoxic to melanocytes than cryotherapy, but clinical trials comparing these therapies are needed. Limitations of HP40 are its low efficacy and requirement of multiple treatments, which can result in elevated costs. The application can also be time-consuming, though extenders or even staff members can apply it. Therefore, HP40 may be better reserved for the treatment of facial SKs. Introduction Seborrheic keratoses (SKs) are benign epithelial tumors estimated to affect more than 83 million Americans.[1] Existing as at least nine variants, SKs present as round to oval macules or papules with variable surface textures that appear "stuck on" and can occur anywhere on the body, except the palms and soles.[2–4] The incidence and frequency of SKs per person increase with age.[4] In one study of Korean males, the authors found that 79% of patients had SKs at age 40 (with 5.5 SKs per patient) compared to 94% of patients at age 50 (with 9.9 SKs per patient).[5] In addition to increasing age, potential risk factors for SKs include ultraviolet light, as they occur with a higher prevalence on sun-exposed skin,[5,6] friction given they commonly occur in intertriginous areas,[7] and genetic predisposition.[7,8] However, the true etiologic risk factors and pathogenesis of SKs are not fully known. Inhibition of apoptosis may occur in SKs, contributing to their formation.[4] Additionally, mutations in the fibroblast growth factor receptor[8] and oncogenic phosphoinositide 3-kinase pathway[9] may impact their development; however, these changes are not present in all SKs so additional genes are likely involved.[8] While SKs do not require treatment, patients often request removal to relieve symptoms of irritated SKs or for cosmetic reasons.[10] The most common treatment is cryotherapy with liquid nitrogen; surgical therapies are also used including electrodessication, curettage, shave excision, or laser therapy.[7,11] Among other side effects, these invasive methods can cause pain, bleeding, pigmentary changes, and scarring.[7,12–15] The risk of pigmentary changes is especially high in patients with skin of color.[7] These side effects motivated the pursuit for efficacious topical therapies that minimize long-term adverse effects. Existing keratolytics (ammonium lactate, imiquimod, and tazarotene) and vitamin D analogs were examined to treat SKs, but these agents demonstrated limited efficacy in small clinical trials.[16–19] The first topical therapy to be US FDA-approved for the treatment of raised SKs is HP40 (Eskata™), a stabilized topical solution of 40% hydrogen peroxide (H2O2).[20] This therapy was approved in December 2017 based on the results of two phase 3 trials.[20] An earlier phase 2 dose-ranging trial additionally confirmed that HP40 was more efficacious than 32% H2O2 while still having a satisfactory side effect profile.[21] In this review, we will discuss the evidence for and limitations of HP40 based on these clinical trials as well as an ex vivo model of Fitzpatrick Skin Type (FST) V skin that examined HP40's cytotoxicity.
