Enhancing Outcomes in Seborrheic Keratosis: Using a Novel Treatment Solution

Seborrheic keratosis (SK) is one of the most common cutaneous lesions that a dermatologist will encounter daily.¹ SKs can develop anywhere on the body excluding the soles, palms, and mucous membranes.1 SKs are benign epithelial tumors that present as “stuck-on”, well-demarcated, waxy, or verrucous papules or plaques that consist of varying coloration from flesh-colored to heavily pigmented (brown, yellow, grey, or black).² SKs appear most commonly in middle-aged individuals, 31-50 years (42%), and the number and size of SKs increases with age.³ One study conducted in Australia reported that the prevalence of SKs increased from 12% of individuals between 15-25 years old to 100% in individuals over the age of 50.4 Within the same study, the average number of lesions increased from 6 lesions per individual in the age group of 15-25 years old to 69 lesions per individual in the group that was 75 years or older.⁴ Even though studies indicate that the incidence of SKs increases with age, the etiopathology is still misunderstood.⁵ Age, chronic ultra-violet (UV) exposure, and genetic inheritance are commonly proposed hypotheses that are associated with the occurrence of SKs. SKs can appear anywhere on the body, but one study of 406 total patients found the majority of SKs were found on the truncal region (chest, back, shoulders, abdomen) in approximately 85% of patients, and the face in approximately 68% of the patients.⁶

Typically, SKs present with dermoscopic findings such as fissures and ridges, hairpin vessels with white halo, comedo-like openings, and milia-like cysts.7 Fissures and ridges are terms used to describe the linear grooves produced in the epidermis that present as thick, curved lines giving the lesion a “brain-like” appearance.⁸ Hairpin vessels are characterized by linear vessels that form a U-shape with a bend at one end resembling a hairpin with a whitish halo surrounding the vessels.^7,8 Comedo-like openings are keratin-filled invaginations of the epidermis and appear as black or brown, roundish structures.^7,8 Finally, milia-like cysts are characterized by round white to yellowish globules.^7,8

The presence of these dermoscopic findings correspond with the histopathologic changes within the epidermis and dermis. The thickened, papillomatous surface of the epidermis forms grooves and clefts that can be filled with keratin. The intralesional cysts of loose filled keratin cleft are called pseudohorn cysts and correlate to the appearance comedo-like openings of the SK.^7,9,10 The presence of intraepidermal cysts signify milia-like cysts, while the appearance of hairpin vessels are caused by enlarged capillaries within the dermis.^7,9,10

The majority of SKs are typically asymptomatic and benign, therefore, do not require removal, but patients will often choose to have these lesions removed. The truncal regions are subject to frequent contact by clothing fabric, which may cause SKs to become symptomatic resulting in irritation, pain, bleeding, or itching.¹¹ Patients also elect for removal of SKs for cosmetic reasons, often stating a desire to improve their quality of life

and maintain a more youthful appearance since SKs are often termed “age-spots”.¹¹ One study specifically reported that 61% of the female patients attempted to conceal or disguise the appearance of SKs by using specific clothing, hairstyles, and even make-up.⁶ The majority of SKs are removed or treated for cosmetic purposes. Treatment methods include cryosurgery, electrodessication, shave excision, curettage, and emerging topical treatment, such as hydrogen peroxide topical solution (HP40) (Eskata™, Aclaris Therapeutics, Wayne, PA).

The most common traditional technique for SK removal is with the use of cryosurgery.¹² Although the specific mechanism of cryosurgery is not fully understood, cryosurgery destroys the SK lesion by inducing intracellular ice crystal formation within the benign tissue, which leads to various inflammatory responses.^13-15 Cryosurgery can be effective for SK removal depending on characteristics of the lesions and patient, freezing technique, freezing time, and the number of freeze/thaw cycles.^11,12 Larger and thicker lesions will often require extended freezing durations or more treatment sessions compared to small flat SKs.11 Another commonly employed technique used by dermatologists is electrosurgery, which uses an electrode held at a certain distance away from the skin that creates a local energy delivery specifically destroying the epidermal tissue.¹¹ Curettage is another technique that can be used in combination with both electrosurgery or cryosurgery to remove any remaining SK lesions.¹¹ A study done by Wood et al. reported that 64% of the patients who had their SK lesions treated by cryosurgery or curettage, preferred cryosurgery due to a decreased amount of postoperative wound care after cryosurgery.¹⁶ Adverse effects such as erythema, slight bleeding, blister formation, and pain are typically found at the treatment site after both treatments. However, both treatments can cause potential long-term complications such as scarring, permanent pigmentation changes (hyper or hypopigmentation), infection, and lesion recurrence.¹⁷ Patients with darker skin types have an increased likelihood of pigmentary changes, recurrence, and scarring compared to individuals with a lighter skin type.^11,15

Due to many of these concerns of adverse effects and postoperative care, patients have expressed interest in a noninvasive, safe, cosmetically acceptable treatment for SK removal.¹⁸ Patients indicated that they avoided the removal of SKs due to potential long-term side effects such as scarring, discomfort, pain, and post-treatment hypo or hyperpigmentation.6 Recently, the US Food and Drug Administration approved a hydrogen peroxide topical solution 40% (HP40; Eskata) as the first and only topical treatment for raised SKs. The high concentration of hydrogen peroxide within the topical solution can produce reactive hydroxyl radicals and other oxygen species that cause oxidative damage to the SKs.^17-20 However, the exact mechanism of action for HP40 is unknown. Although a similar adverse effect profile as traditional therapies may be seen using HP40, a recent ex vivo study compared cryosurgery and HP40, concluding that HP40 caused less cytotoxicity and reduced melanocyte damage than cryosurgery.²¹ The authors suggested that HP40 is a safer option for SK removal that features a decrease in posttreatment pigmentary alteration.^19,21 Two randomized, double-blind, placebo-controlled studies evaluated the safety and efficacy of hydrogen peroxide topical solution on patients with seborrheic keratosis. After day 106, lesions undergoing two treatments with hydrogen peroxide resulted in scarring, hypopigmentation, and hyperpigmentation in <1%, 3.0%, and 7.8% of lesions, respectively.²² The authors also found that the percentage of subjects achieving clearance of all four target lesions at day 106 were 4% and 8% while the percentage of subjects in which 3 of 4 target lesions were “clear” was 13% and 23%.²² Here, we report the methods and results from an HP40 treatment for two individuals.

Patient one, a 73-year-old female with Fitzpatrick skin type III, stated that she has an extensive history of sun exposure throughout her youth and adulthood. The individual reported that she began to notice the appearance of her SKs approximately 30 years ago on her chest and back region, and she had seen that the number and size of the SKs slowly began to increase over the years. Patient one stated that she has been continuously bothered by the appearance of the SKs indicating that they appear “ugly and unappealing,” and made her skin seem “aged,” which affected how she perceived her image. She expressed dislike in the color and texture of the SKs, and due to the appearance, she believes that when people saw her, they thought she was older than her actual age. She also noted that the SKs are sometimes irritating, producing discomfort. Patient one explained that she previously had traditional treatments, including cryosurgery, and excision, for the cosmetic removal of her SKs, after which she experienced moderate to severe adverse effects. Adverse effects included erythema, blistering, tenderness, and hypopigmentation that mostly resolved after 1 week to 2 months. She indicated that she had noticed some residual post-treatment hypopigmentation in the areas treated with traditional therapies. The patient explained that she scheduled an appointment to talk about the removal of her SKs, and during the appointment, she was introduced to the hydrogen peroxide topical solution called Eskata. The patient stated that she became very interested in Eskata due to it being an alternative, non-invasive treatment compared to the traditional treatment. The patient revealed that she tolerated the initial treatment well with a slight amount of irritation. The patient expressed after the treatment there were very mild adverse effects such as, blistering, redness, and tenderness, for approximately 1 week with no evidence of post-treatment hypopigmentation. In comparing HP40 with her previous treatments, the patient stated the side effects with the HP40 were less overall, but she noted the areas targeted were smaller compared to her other