to the chest and abdomen,16 suggesting that a reduced barrier function may augment the penetration of HP40 on the face. In addition, the lipid content from sebum production on the face17,18 may also enhance the treatment effect of HP40. Another explanation is that because SKs on the face are exposed more often to ultraviolet radiation; their ultraviolet damage signatures may have impaired salvage pathways when subjected to oxidation induced by HP40.1,19,20 The differential benefit of HP40 on facial SKs is relevant, given that smaller and thinner lesions on cosmetically sensitive locations are the most challenging to manage with cryosurgery. Finally, facial SKs tend to be smaller and thinner compared with lesions on the trunk or extremities, although baseline lesion size stratified by length x width of SKs (25-100 mm2 vs >100 mm2) in this study was similar, regardless of anatomic location. In addition, baseline thickness by PLA (≤1 mm vs >1 mm) was similar for SKs on the face and extremities.21 While the exact mechanism of action of HP40 topical solution in the removal of SKs has not been characterized, the chemical and physical properties of hydrogen peroxide have been studied extensively since it was first described by the French chemist Louis-Jacques Thénard in 1818.22 We hypothesize that the high concentration of hydrogen peroxide solution, upon penetration into an SK lesion, generates reactive oxygen species leading to lipid and membrane peroxidation with membrane lysis; protein oxidation, which tends to favor necrotic cell damage/death; and ultimately, DNA damage via site-specific hydroxyl formation, thiol oxidation, and mitochondrial membrane damage, which tend to favor apoptosis.There are several limitations that must be noted in this analysis. First, a sub-stratification of extremity locations (eg, dorsum of the hand versus forearm) and trunk (eg, neck vs back) was not conducted. SKs also present as various histologic subtypes, which are not reliably predictable from clinical appearance. All SKs in this trial were required to be raised but subtyping of SK variants was not performed (ie, no biopsies were obtained) and the size limitation to a minimum of 5 mm diameter and raised thickness excluded common variants such as dermatosis papulosa nigra and macular SKs, respectively. Further work will evaluate patient satisfaction with HP40 treatment and will be correlated with treatment outcomes including the physician-graded PLA score.23
The recent FDA-approved 40% (w/w) hydrogen peroxide topical solution in a single-use applicator represents a novel SK treatment option for providers to offer to their patients. The highest treatment effect and the lowest risk of dyspigmentation with HP40 versus vehicle was observed on facial SKs, which also cleared at the highest rate after a single treatment. Most common immediate reactions with HP40 were erythema, stinging stinging, and edema, which resolved to none or mostly mild within a week.
Dr. Smith has served on advisory boards for Aclaris Therapeutics. Dr. Xu is a consultant to Aclaris Therapeutics. Dr. Estes and Shanler are employed by Aclaris Therapeutics. Funding/Support: This study was supported by Aclaris Therapeutics, Inc.
The authors would like to acknowledge Julia Bohnenberger, Vanesha Patel, Matt Stroschein, Mark Bradshaw, David Gordon, and the patients who participated in this study for their assistance with and support of this study.
- Heidenreich B, Denisova E, Rachakonda S, et al. Genetic alterations in seborrheic keratoses. Oncotarget. 2017;8:36639-36649.
- Neel VA, Todorova K, Wang J, et al. Sustained Akt activity is required to maintain cell viability in seborrheic keratosis, a benign epithelial tumor. J Invest Dermatol. 2016;136:696-705.
- Hafner C, Lopez-Knowles E, Luis NM, et al. Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern. Proc Natl Acad Sci U S A. 2007;104:13450-13454.
- Logie A, Dunois-Larde C, Rosty C, et al. Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans. Hum Mol Genet. 2005;14:1153-1160.
- Lim HW, Collins SAB, Resneck JS, Jr., et al. The burden of skin disease in the United States. J Am Acad Dermatol. 2017;76:958-972 e952.
- Hafner C, Vogt T. Seborrheic keratosis. J Dtsch Dermatol Ges. 2008;6:664- 677.
- Baumann L, Blauvelt A, Draelos Z, et al. Safety and efficacy of hydrogen peroxide topical solution, 40% (w/w) in patients with seborrheic keratoses: results from two identical, randomized, double-blind, placebo-controlled, phase 3 studies (A-101-SEBK-301/302). J Am Acad Dermatol. 2018. doi: 10.1016/j.jaad.2018.05.044.
- DuBois JC, Jarratt M, Beger BB, et al. A-101, a proprietary topical formulation of high-concentration hydrogen peroxide solution: A randomized, double-blind, vehicle-controlled, parallel group study of the dose-response profile in subjects with seborrheic keratosis of the face. Dermatol Surg. 2018;44:330- 340.
- Jackson JM, Alexis A, Berman B, et al. Current understanding of seborrheic keratosis: Prevalence, etiology, clinical presentation, diagnosis, and management. J Drugs Dermatol. 2015;14:1119-1125.
- Tay YK, Tan SK. A study comparing the efficacy and risk of adverse events using two techniques of electrocautery for the treatment of seborrheic keratoses. Dermatol Surg. 2013;39:810-813.
- Herron MD, Bowen AR, Krueger GG. Seborrheic keratoses: a study comparing the standard cryosurgery with topical calcipotriene, topical tazarotene, and topical imiquimod. Int J Dermatol. 2004;43:300-302.
- Kee CE. Liquid nitrogen cryotherapy. Arch Dermatol. 1967;96:198-203.
- Burkhart CG. The search for topical treatments for seborrheic keratoses continues. Int J Dermatol. 2006;45:1110.
- Klaus MV, Wehr RF, Rogers RS, 3rd, et al. Evaluation of ammonium lactate in the treatment of seborrheic keratoses. J Am Acad Dermatol. 1990;22:199- 203.
- Darlenski R, Fluhr JW. Influence of skin type, race, sex, and anatomic location on epidermal barrier function. Clin Dermatol. 2012;30:269-273.
- Lee Y, Hwang K. Skin thickness of Korean adults. Surg Radiol Anat. 2002;24:183-189.
- Sadowski T, Klose C, Gerl MJ, et al. Large-scale human skin lipidomics by quantitative, high-throughput shotgun mass spectrometry. Sci Rep. 2017;7:43761.
- Greene RS, Downing DT, Pochi PE, et al. Anatomical variation in the amount and composition of human skin surface lipid. J Invest Dermatol. 1970;54:240-247.
- Rebel H, Kram N, Westerman A, et al. Relationship between UV-induced mutant p53 patches and skin tumours, analysed by mutation spectra and by induction kinetics in various DNA-repair-deficient mice. Carcinogenesis. 2005;26:2123-2130.
- de Gruijl FR, van der Leun JC. Development of skin tumors in hairless mice after discontinuation of ultraviolet irradiation. Cancer Res. 1991;51:979-984.
- Data on file. Aclaris Therapeutics, Inc.
- Thénard LJ. Observations sur des nouvelles combinaisons entre l'oxigène et divers acides. Ann Chim Phys (Paris). 1818;2:306-312.
- Clinicaltrials.gov. A study assessing subject satisfaction with A-101 topical solution for seborrheic keratoses (SK-FAN). https://clinicaltrials.gov/ct2/ show/NCT03487588. Accessed April 4, 2018.
Esther Estes MD MPH email@example.com