Clinical Experience With 40% Hydrogen Peroxide Topical Solution for the Treatment of Seborrheic Keratosis

July 2019 | Volume 18 | Issue 7 | Supplement Individual Articles | 173 | Copyright © July 2019


Marina Peredo MD,ª Emily Murphy BS,b,c Damira Karibayeva MDa

aSkinfluence, New York, NY

bDepartment of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC

cSchool of Medicine, Georgetown University, Washington, DC

treated with one HP40 pen according to the manufacturer’s protocol. At a follow-up visit six weeks later (Figure 2B), residual disease was present, so all the SKs were retreated with HP40. Four weeks later (70 days after the first treatment), the SKs were nearly clear without scarring, an outcome that pleased the patient (Figure 2C).

DISCUSSION

HP40 was recently FDA-approved to treat raised SKs and as demonstrated by the two cases presented here, this in-office treatment can lead to positive therapeutic outcomes for SKs located in cosmetically-sensitive areas. The mechanism by which HP40 destroys SKs is not fully understood, but it likely utilizes the oxidizing potential of H2O2.28 H2O2 can directly damage cell components as a reactive oxygen species and form hydroxyl free radicals to exert further oxidative damage.29 Applied at supraphysiologic doses, HP40 delivers a fraction of the dose through the stratum corneum (SC) to the epidermis, where it can generate free radicals by overcoming the skin’s antioxidant capabilities and initiate cellular apoptosis and necrosis. Because of this mechanism, HP40 should not be applied to open or infected SKs where the SC is compromised. The SC protects deep tissue from high concentration H2O2 so without this barrier, H2O2 can cause rapid death of nearby cells.30 However, when used properly in phase 3 trials, side effects of HP40 were limited to local skin reactions, the majority being mild to moderate.26 Scarring, hypopigmentation, and hyperpigmentation occurred in less than 1%, 3.0%, and 7.8% of sites treated with HP40, respectively.26 Although, nearly all of the participants were Fitzpatrick Skin Types I to IV, so the effect of HP40 on darker skin is less clear.26 In an ex vivo model of human Fitzpatrick Skin Type V, HP40 was less toxic to melanocytes compared to cryotherapy.31 Therefore, HP40 may be superior to cryotherapy for skin of color, but large, controlled studies including multiple skin types are needed to compare these therapies. 

In support of HP40’s potential to minimize the risk of scarring and pigmentary changes, the patient in Case 1 was previously treated with cryotherapy, which led to hypopigmented scarring. However, as seen in Figure 1D, there was no evidence of scarring or hypopigmentation from HP40 after over three months. The patient in Case 2 with Fitzpatrick Skin Type IV was similarly spared of these adverse effects. While HP40 still has a small risk of scarring and pigmentary changes, this is a good option to discuss with patients who want to minimize the side effects from treating SKs in visible skin areas. 

Selecting a therapeutic strategy for SK removal requires consideration of the location of SKs as well as the patient’s skin type and expectations of what will be left behind after removal. Given HP40 is not covered by insurance and multiple treatments may be needed, patients with SKs in non-cosmetically sensitive areas may prefer treatment with cryotherapy, curettage, or electrodessication. However, patients with SKs in cosmeticallysensitive areas like the face and neck, particularly those with dark skin types, may benefit from a topical therapy like HP40 that is less cytotoxic to melanocytes and the neighboring epidermis. 31 This is especially true if patients are dissatisfied with previous treatments. Further, as demonstrated by phase 3 trials26 and based on the author’s experience, raised SKs on the face and neck respond especially well to treatment with HP40.

In addition to instructions provided by the manufacturer, the following practical considerations based on the author’s experience may be helpful when using HP40. It is important to apply firm pressure and cover the entire lesion, while staying within a 2 to 3 millimeter margin of the SK to avoid contact with normal skin. Four treatment cycles are recommended for each SK, but if the patient experiences 6 to 7 or more pain on a scale of 0 to 10, the treatment should be terminated. Additionally, when treating SKs near the orbital rim, some eyelid swelling is expected; reassure the patient that this usually resolves in a few hours.

Overall, HP40 is a new therapeutic option for SKs that can be discussed with patients. As demonstrated by the cases presented here, HP40 is particularly useful for SKs on the face and neck and may avoid the scarring and hypopigmentation that can occur with cryotherapy. Future examination of HP40 in patients with dark skin types is needed to confirm our suspicion that HP40 may lead to less pigmentary changes than non-topical, invasive therapies. 

DISCLOSURE

The authors have no conflicts of interest.

REFERENCES

  1. Bickers D, Lim H, Margolis D, et al. The burden of skin diseases: 2004 a joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology. J Am Acad Dermatol. 2006;55(3):490-500.
  2. 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(4):300-302. doi:10.1111/ j.1365-4632.2004.02282.x
  3. Kwon OS, Hwang EJ, Bae JH, et al. Seborrheic keratosis in the Korean males: causative role of sunlight. Photodermatol Photoimmunol Photomed. 2003;19(2):73-80.
  4. Yeatman JM, Kilkenny M, Marks R. The prevalence of seborrhoeic keratoses in an Australian population: does exposure to sunlight play a part in their frequency? Br J Dermatol. 1997;137(3):411-414.
  5. Jackson JM, Alexis A, Berman B, Berson DS, Taylor S, Weiss JS. Current understanding of seborrheic keratosis: prevalence, etiology, clinical presentation, diagnosis, and management. J Drugs Dermatol. 2015;14(10):1119-1125.
  6. Noiles K, Vender R. Are all seborrheic keratoses benign? Review of the typical lesion and its variants. J Cutan Med Surg. 2008;12(5):203-210. doi:10.2310/7750.2008.07096
  7. Logié A, Dunois-Lardé 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(9):1153-1160. doi:10.1093/hmg/ddi127
  8. Hafner C, López-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 USA. 2007;104(33):13450-13454. doi:10.1073/pnas.0705218104
  9. Nakamura S, Nishioka K. Enhanced expression of p16 in seborrhoeic kera Dermatol. 2003;149(3):560-565.
  10. Hafner C, Hartmann A, van Oers JMM, et al. FGFR3 mutations in seborrheic keratoses are already present in flat lesions and associated with age and localization. Mod Pathol. 2007;20(8):895-903. doi:10.1038/modpathol.3800837
  11. Li Y-H, Chen G, Dong X-P, Chen H-D. Detection of epidermodysplasia verruciformis-associated human papillomavirus DNA in nongenital seborrhoeic keratosis. Br J Dermatol. 2004;151(5):1060-1065. doi:10.1111/j.1365- 2133.2004.06244.x
  12. Kennedy C, Bajdik CD, Willemze R, De Gruijl FR, Bouwes Bavinck JN, Leiden Skin Cancer Study. The influence of painful sunburns and lifetime sun exposure on the risk of actinic keratoses, seborrheic warts, melanocytic nevi, atypical nevi, and skin cancer. J Invest Dermatol. 2003;120(6):1087-1093. doi:10.1046/j.1523-1747.2003.12246.x
  13. Del Rosso JQ. A Closer look at seborrheic keratoses: patient perspectives, clinical relevance, medical necessity, and implications for management. J Clin Aesthet Dermatol. 2017;10(3):16-25.
  14. Ranasinghe GC, Friedman AJ. Managing seborrheic keratoses: evolving strategies for optimizing patient outcomes. J Drugs Dermatol. 2017;16(11):1064- 1068.
  15. Mehrabi D, Brodell RT. Use of the alexandrite laser for treatment of seborrheic keratoses. Dermatol Surg. 2002;28(5):437-439.
  16. Wood LD, Stucki JK, Hollenbeak CS, Miller JJ. Effectiveness of cryosurgery vs curettage in the treatment of seborrheic keratoses. JAMA Dermatol. 2013;149(1):108-109. doi:10.1001/2013.jamadermatol.275
  17. Andrews MD. Cryosurgery for common skin conditions. Am Fam Physician. 2004;69(10):2365-2372.
  18. Kundu RV, Joshi SS, Suh K-Y, et al. Comparison of electrodesiccation and potassium-titanyl-phosphate laser for treatment of dermatosis papulosa nigra. Dermatol Surg. 2009;35(7):1079-1083. doi:10.1111/j.1524-4725.2009.01186.x
  19. Ferrandiz L, Moreno-Ramirez D, Camacho FM. Shave excision of common acquired melanocytic nevi: cosmetic outcome, recurrences, and complications. Dermatol Surg. 2005;31(9 Pt 1):1112-1115.
  20. Kim YK, Kim D-Y, Lee SJ, Chung WS, Cho SB. Therapeutic efficacy of long-pulsed 755-nm alexandrite laser for seborrheic keratoses. J Eur Acad Dermatol Venereol. 2014;28(8):1007-1011. doi:10.1111/jdv.12231
  21. Culbertson GR. 532-nm diode laser treatment of seborrheic keratoses with color enhancement. Dermatol Surg. 2008;34(4):525-528; discussion 528. doi:10.1111/j.1524-4725.2007.34098.x
  22. Stockfleth E, Röwert J, Arndt R, Christophers E, Meyer T. Detection of human papillomavirus and response to topical 5% imiquimod in a case of stucco keratosis. Br J Dermatol. 2000;143(4):846-850.
  23. Klaus MV, Wehr RF, Rogers RS, Russell TJ, Krochmal L. Evaluation of ammonium lactate in the treatment of seborrheic keratoses. J Am Acad Dermatol. 1990;22(2 Pt 1):199-203.
  24. Mitsuhashi Y, Kawaguchi M, Hozumi Y, Kondo S. Topical vitamin D3 is effective in treating senile warts possibly by inducing apoptosis. J Dermatol. 2005;32(6):420-423.
  25. Levy-Nissenbaum E, Thio HB, Burstein P, Thaci D. Seborrhoeic keratosis removal in a multicentre phase I/II clinical trial using a novel topical formulation (BL-5010). Br J Dermatol. 2015;173(1):247-249. doi:10.1111/bjd.13623
  26. Baumann LS, Blauvelt A, Draelos ZD, et al. Safety and efficacy of hydrogen peroxide topical solution, 40% (w/w), in patients with seborrheic keratoses: Results from 2 identical, randomized, double-blind, placebo-controlled, phase 3 studies (A-101-SEBK-301/302). J Am Acad Dermatol. 2018;79(5):869- 877. doi:10.1016/j.jaad.2018.05.044
  27. Smith S, Xu S, Estes E, Shanler S. Anatomic Site-specific treatment response with 40% hydrogen peroxide (w/w) topical formulation for raised seborrheic keratoses: pooled analysis of data from two phase 3 studies. J Drugs Dermatol. 2018;17(10):1092-1098.
  28. Kao S, Kiss A, Efimova T, Friedman AJ. Managing seborrheic keratosis: evolving strategies and optimal therapeutic outcomes. J Drugs Dermatol. 2018;17(9):933-940.
  29. Young I, Woodside J. Antioxidants in health and disease. J Clin Pathol. 2001;54(3):176-186. doi:10.1136/jcp.54.3.176
  30. Bito T, Izu K, Tokura Y. Evaluation of toxicity and Stat3 activation induced by hydrogen peroxide exposure to the skin in healthy individuals. J Dermatol Sci. 2010;58(2):157-159. doi:10.1016/j.jdermsci.2010.03.013
  31. Kao S, Kiss A, Efimova T, Friedman A. Ex vivo evaluation of cytotoxicity and melanocyte viability after A-101 hydrogen peroxide topical solution 40% or cryosurgery treatment in seborrheic keratosis lesions. J Am Acad Dermatol. 2018;79(4):767-768. doi:10.1016/j.jaad.2018.03.034
  32. Zouboulis CC. Principles of cutaneous cryosurgery: an update. Dermatology (Basel). 1999;198(2):111-117. doi:10.1159/000018084
  33. Hafner C, Vogt T. Seborrheic keratosis. J Dtsch Dermatol Ges. 2008;6(8):664- 677. doi:10.1111/j.1610-0387.2008.06788.x
  34. DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 . Record No. T907421, Ammonium Lactate. http://www.dynamed.com/topics/ dmp~AN~T907421/Ammonium-Lactate. Published October 8, 2018. Accessed March 16, 2019.

AUTHOR CORRESPONDENCE

Emily Murphy BS ecm101@georgetown.edu